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Retraction Note: pH-responsive CAP-co-poly(methacrylic acid)-based hydrogel as an efficient platform for controlled gastrointestinal delivery: fabrication, characterization, in vitro and in vivo toxicity evaluation

Shah SA, Sohail M, Minhas MU, Nisar-Ur-Rehman, Khan S, Hussain Z, et al.

Drug Deliv Transl Res, 2024 Apr 11.
PMID: 38602616 DOI: 10.1007/s13346-024-01600-2
Correction to: Domperidone nanocrystals with boosted oral bioavailability: fabrication, evaluation and molecular insight into the polymer-domperidone nanocrystal interaction

Ndlovu ST, Ullah N, Khan S, Ramharack P, Soliman M, de Matas M, et al.

Drug Deliv Transl Res, 2024 Feb 28.
PMID: 38416387 DOI: 10.1007/s13346-024-01554-5
Synthesis of Electrical Conductive Metal-Organic Frameworks for Electrochemical Applications

Shoaib Ahmad Shah S, Altaf Nazir M, Mahmood A, Sohail M, Ur Rehman A, Khurram Tufail M, et al.

Chem Rec, 2024 Jan;24(1):e202300141.
PMID: 37724006 DOI: 10.1002/tcr.202300141

Electrical conductivity is very important property of nanomaterials for using wide range of applications especially energy applications. Metal-organic frameworks (MOFs) are notorious for their low electrical conductivity and less considered for usage in pristine forms. However, the advantages of high surface area, porosity and confined catalytic active sites motivated researchers to improve the conductivity of MOFs. Therefore, 2D electrical conductive MOFs (ECMOF) have been widely synthesized by developing the effective synthetic strategies. In this article, we have summarized the recent trends in developing the 2D ECMOFs, following the summary of potential applications in the various fields with future perspectives.
Team-based self-directed learning enhanced students' learning experience in undergraduate surgical teaching

Sim SK, Myo N, Sohail M

Med J Malaysia, 2023 Jan;78(1):61-67.
PMID: 36715193

INTRODUCTION: To evaluate the effectiveness of team-based self-directed learning (SDL) in the teaching of the undergraduate Year 5 surgical posting.
MATERIALS AND METHODS: A quasi-experimental study was conducted to develop and administer a team-based SDL versus a conventional SDL to teach undergraduate surgical topics. One hundred and seventy-four medical students who underwent the Year 5 surgical posting were recruited. They were assigned to two groups receiving either the teambased SDL or the conventional SDL. Pre- and post-SDL assessments were conducted to determine students' understanding of selected surgical topics. A selfadministered questionnaire was used to collect student feedback on the team-based SDL.
RESULTS: The team-based SDL group scored significantly higher than the conventional SDL group in the post-SDL assessment (74.70 ± 6.81 vs. 63.77 ± 4.18, t = -12.72, p < 0.01). The students agreed that the team-based SDL method facilitated their learning process.
CONCLUSION: The study demonstrated that the use of a teambased SDL is an effective learning strategy for teaching the Year 5 surgical posting. This method encouraged peer discussion and promoted teamwork in completing task assignments to achieve the learning objectives.
A Targeted Review of Current Progress, Challenges and Future Perspective of g-C3 N4 based Hybrid Photocatalyst Toward Multidimensional Applications

Hayat A, Sohail M, Anwar U, Taha TA, Qazi HIA, Amina, et al.

Chem Rec, 2023 Jan;23(1):e202200143.
PMID: 36285706 DOI: 10.1002/tcr.202200143

The increasing demand for searching highly efficient and robust technologies in the context of sustainable energy production totally rely onto the cost-effective energy efficient production technologies. Solar power technology in this regard will perceived to be extensively employed in a variety of ways in the future ahead, in terms of the combustion of petroleum-based pollutants, CO2 reduction, heterogeneous photocatalysis, as well as the formation of unlimited and sustainable hydrogen gas production. Semiconductor-based photocatalysis is regarded as potentially sustainable solution in this context. g-C3 N4 is classified as non-metallic semiconductor to overcome this energy demand and enviromental challenges, because of its superior electronic configuration, which has a median band energy of around 2.7 eV, strong photocatalytic stability, and higher light performance. The photocatalytic performance of g-C3 N4 is perceived to be inadequate, owing to its small surface area along with high rate of charge recombination. However, various synthetic strategies were applied in order to incorporate g-C3 N4 with different guest materials to increase photocatalytic performance. After these fabrication approaches, the photocatalytic activity was enhanced owing to generation of photoinduced electrons and holes, by improving light absorption ability, and boosting surface area, which provides more space for photocatalytic reaction. In this review, various metals, non-metals, metals oxide, sulfides, and ferrites have been integrated with g-C3 N4 to form mono, bimetallic, heterojunction, Z-scheme, and S-scheme-based materials for boosting performance. Also, different varieties of g-C3 N4 were utilized for different aspects of photocatalytic application i. e., water reduction, water oxidation, CO2 reduction, and photodegradation of dye pollutants, etc. As a consequence, we have assembled a summary of the latest g-C3 N4 based materials, their uses in solar energy adaption, and proper management of the environment. This research will further well explain the detail of the mechanism of all these photocatalytic processes for the next steps, as well as the age number of new insights in order to overcome the current challenges.
Personality assessment in military - Bright and dark sides of the assessment measures: A review

Sohail M, Naeem F, Javaid MU, Ibikunle AK

Work, 2023;76(3):979-990.
PMID: 37182851 DOI: 10.3233/WOR-220454

BACKGROUND: Personality assessment has its own bright and dark sides, especially in the military setting. It is at play since the emergence of clinical psychology and its application in the recruitment process during World War I and II. Change in personality assessment trends, the evolution of complex personality traits, and changing geopolitical settings across the world necessitate the development of cost-effective, time-efficient, and reliable assessment measures that overcome issues in current assessment measures and fulfil the needs of present timesOBJECTIVE:The objective of this paper is to explore the evolution of personality assessment measures and their uses in military settings along with the comparison of self-report and non-self-report measures. It would give directions for the development of new measures to overcome the issues and drawbacks associated with current measures of research.
METHODS: The research question was formulated using the most valid SPIDER technique for a comprehensive search. PubMed, Google Scholar, and PsycNet databases were searched. 19 articles were selected based on inclusion and exclusion criteria out of 775 articles.
RESULTS: Thematic analyses show that personality assessment in the military is done to a) detect psychopathology, b) detect aberrant responses, c) recruit new personnel, d) predict training and performance outcomes, and e) predict leadership. The research contributes to the body of knowledge by showing an integrated picture of the most widely used assessment tools and the purpose it serves.
CONCLUSION: There is a need to develop assessment measures that are culture free and can assess more complex personality attributes.
Recent Advancement in Rational Design Modulation of MXene: A Voyage from Environmental Remediation to Energy Conversion and Storage

Hayat A, Sohail M, Qadeer A, Taha TA, Hussain M, Ullah S, et al.

Chem Rec, 2022 Dec;22(12):e202200097.
PMID: 36103617 DOI: 10.1002/tcr.202200097

Use of MXenes (Ti3 C2 Tx ), which belongs to the family of two-dimensional transition metal nitrides and carbides by encompassing unique combination of metallic conductivity and hydrophilicity, is receiving tremendous attention, since its discovery as energy material in 2011. Owing to its precursor selective chemical etching, and unique intrinsic characteristics, the MXene surface properties are further classified into highly chemically active compound, which further produced different surface functional groups i. e., oxygen, fluorine or hydroxyl groups. However, the role of surface functional groups doesn't not only have a significant impact onto its electrochemical and hydrophilic characteristics (i. e., ion adsorption/diffusion), but also imparting a noteworthy effect onto its conductivity, work function, electronic structure and properties. Henceforth, such kind of inherent chemical nature, robust electrochemistry and high hydrophilicity ultimately increasing the MXene application as a most propitious material for overall environment-remediation, electrocatalytic sensors, energy conversion and storage application. Moreover, it is well documented that the role of MXenes in all kinds of research fields is still on a progress stage for their further improvement, which is not sufficiently summarized in literature till now. The present review article is intended to critically discuss the different chemical aptitudes and the diversity of MXenes and its derivates (i. e., hybrid composites) in all aforesaid application with special emphasis onto the improvement of its surface characteristics for the multidimensional application. However, this review article is anticipated to endorse MXenes and its derivates hybrid configuration, which is discussed in detail for emerging environmental decontamination, electrochemical use, and pollutant detection via electrocatalytic sensors, photocatalysis, along with membrane distillation and the adsorption application. Finally, it is expected, that this review article will open up new window for the effective use of MXene in a broad range of environmental remediation, energy conversion and storage application as a novel, robust, multidimensional and more proficient materials.
Recent Advances and Future Perspectives of Metal-Based Electrocatalysts for Overall Electrochemical Water Splitting

Hayat A, Sohail M, Ali H, Taha TA, Qazi HIA, Ur Rahman N, et al.

Chem Rec, 2022 Nov 21.
PMID: 36408911 DOI: 10.1002/tcr.202200149

Recently, the growing demand for a renewable and sustainable fuel alternative is contingent on fuel cell technologies. Even though it is regarded as an environmentally sustainable method of generating fuel for immediate concerns, it must be enhanced to make it extraordinarily affordable, and environmentally sustainable. Hydrogen (H2 ) synthesis by electrochemical water splitting (ECWS) is considered one of the foremost potential prospective methods for renewable energy output and H2 society implementation. Existing massive H2 output is mostly reliant on the steaming reformation of carbon fuels that yield CO2 together with H2 and is a finite resource. ECWS is a viable, efficient, and contamination-free method for H2 evolution. Consequently, developing reliable and cost-effective technology for ECWS was a top priority for scientists around the globe. Utilizing renewable technologies to decrease total fuel utilization is crucial for H2 evolution. Capturing and transforming the fuel from the ambient through various renewable solutions for water splitting (WS) could effectively reduce the need for additional electricity. ECWS is among the foremost potential prospective methods for renewable energy output and the achievement of a H2 -based economy. For the overall water splitting (OWS), several transition-metal-based polyfunctional metal catalysts for both cathode and anode have been synthesized. Furthermore, the essential to the widespread adoption of such technology is the development of reduced-price, super functional electrocatalysts to substitute those, depending on metals. Many metal-premised electrocatalysts for both the anode and cathode have been designed for the WS process. The attributes of H2 and oxygen (O2 ) dynamics interactions on the electrodes of water electrolysis cells and the fundamental techniques for evaluating the achievement of electrocatalysts are outlined in this paper. Special emphasis is paid to their fabrication, electrocatalytic performance, durability, and measures for enhancing their efficiency. In addition, prospective ideas on metal-based WS electrocatalysts based on existing problems are presented. It is anticipated that this review will offer a straight direction toward the engineering and construction of novel polyfunctional electrocatalysts encompassing superior efficiency in a suitable WS technique.
Recent Advancement of the Current Aspects of g-C3 N4 for its Photocatalytic Applications in Sustainable Energy System

Hayat A, Sohail M, Ali Shah Syed J, Al-Sehemi AG, Mohammed MH, Al-Ghamdi AA, et al.

Chem Rec, 2022 Feb 09.
PMID: 35138017 DOI: 10.1002/tcr.202100310

Being one of the foremost enticing and intriguing innovations, heterogeneous photocatalysis has also been used to effectively gather, transform, and conserve sustainable sun's radiation for the production of efficient and clean fossil energy as well as a wide range of ecological implications. The generation of solar fuel-based water splitting and CO2 photoreduction is excellent for generating alternative resources and reducing global warming. Developing an inexpensive photocatalyst can effectively split water into hydrogen (H2 ), oxygen (O2 ) sources, and carbon dioxide (CO2 ) into fuel sources, which is a crucial problem in photocatalysis. The metal-free g-C3 N4 photocatalyst has a high solar fuel generation potential. This review covers the most recent advancements in g-C3 N4 preparation, including innovative design concepts and new synthesis methods, and novel ideas for expanding the light absorption of pure g-C3 N4 for photocatalytic application. Similarly, the main issue concerning research and prospects in photocatalysts based g-C3 N4 was also discussed. The current dissertation provides an overview of comprehensive understanding of the exploitation of the extraordinary systemic and characteristics, as well as the fabrication processes and uses of g-C3 N4 .
Jejunal gastrointestinal stromal tumour masquerading as an ovarian cancer: A case report

Sohail M, Chua RHB, Sim SK, Nik Azim NA

Med J Malaysia, 2022 Jan;77(1):125-127.
PMID: 35087013

A 60-year-old lady presented with lower abdominal discomfort and a huge palpable intra-abdominal mass for 4 months, with significant weight loss over half a year. Transvaginal ultrasonography and computed tomography (CT) abdomen showed a large right solid cystic mass likely ovarian in origin. The CA-125 was raised. With the provisional diagnosis of ovarian cancer patient underwent laparotomy at Hospital Umum Sarawak, Malaysia. However intraoperative findings showed that uterus and both ovaries were normal. The tumour was arising from the jejunum and adherent to the dome of the urinary bladder and right broad ligament. The tumour was resected and final diagnosis was jejunal gastrointestinal stromal tumour (GIST). We described this case which was misinterpreted as an ovarian cancer.
Fulltext Potential application of nanotechnology in the treatment, diagnosis, and prevention of schistosomiasis

Qadeer A, Ullah H, Sohail M, Safi SZ, Rahim A, Saleh TA, et al.

Front Bioeng Biotechnol, 2022;10:1013354.
PMID: 36568300 DOI: 10.3389/fbioe.2022.1013354

Schistosomiasis is one of the neglected tropical diseases that affect millions of people worldwide. Globally, it affects economically poor countries, typically due to a lack of proper sanitation systems, and poor hygiene conditions. Currently, no vaccine is available against schistosomiasis, and the preferred treatment is chemotherapy with the use of praziquantel. It is a common anti-schistosomal drug used against all known species of Schistosoma. To date, current treatment primarily the drug praziquantel has not been effective in treating Schistosoma species in their early stages. The drug of choice offers low bioavailability, water solubility, and fast metabolism. Globally drug resistance has been documented due to overuse of praziquantel, Parasite mutations, poor treatment compliance, co-infection with other strains of parasites, and overall parasitic load. The existing diagnostic methods have very little acceptability and are not readily applied for quick diagnosis. This review aims to summarize the use of nanotechnology in the treatment, diagnosis, and prevention. It also explored safe and effective substitute approaches against parasitosis. At this stage, various nanomaterials are being used in drug delivery systems, diagnostic kits, and vaccine production. Nanotechnology is one of the modern and innovative methods to treat and diagnose several human diseases, particularly those caused by parasite infections. Herein we highlight the current advancement and application of nanotechnological approaches regarding the treatment, diagnosis, and prevention of schistosomiasis.
Fulltext Psychosocial safety climate and self-efficacy: Moderating role of job-related expectations in Pakistani private-sector employees during the COVID-19 pandemic

Maqsood S, Sohail M, Naeem F, Nazri M, Fatima D

Front Psychol, 2022;13:1016050.
PMID: 36926534 DOI: 10.3389/fpsyg.2022.1016050

The labor force in Pakistan comprises 59.8 million individuals. The employees have faced major changes in work dynamics and psychosocial safety climate during the COVID-19 pandemic. The purpose of the current study is to find the relationship between psychosocial safety climate, self-efficacy, and job-related expectations. It explores the moderating role of job-related expectations on the relationship between psychosocial safety climate and self-efficacy. It was hypothesized that there is likely to be a significant relationship between psychosocial safety climate, self-efficacy, and job-related expectations, job-related expectations are likely to moderate the relationship between psychosocial safety climate and self-efficacy, and there are likely to be differences between married and unmarried employees; men and women; satisfied and unsatisfied employees with respect to psychosocial safety, self-efficacy, and job-related expectations. A correlational research design and a convenience sampling strategy were used. A total of 281 employees (M = 30.74 years, SD = 10.99) of the private-sector (including educational, industrial, and IT) organizations during the COVID-19 pandemic were part of the study. Results show that psychosocial safety climate had a positive significant relationship with job-related expectations and self-efficacy. Job expectations also significantly correlated with self-efficacy. There were significant differences in measures of study variables with respect to gender, marital status, and employee satisfaction. This research has implications for administration, managers, policymakers, and organizational psychologists.
Fulltext Nanostructure Engineering via Intramolecular Construction of Carbon Nitride as Efficient Photocatalyst for CO2 Reduction

Sohail M, Altalhi T, Al-Sehemi AG, Taha TAM, S El-Nasser K, Al-Ghamdi AA, et al.

Nanomaterials (Basel), 2021 Nov 29;11(12).
PMID: 34947595 DOI: 10.3390/nano11123245

Light-driven heterogeneous photocatalysis has gained great significance for generating solar fuel; the challenging charge separation process and sluggish surface catalytic reactions significantly restrict the progress of solar energy conversion using a semiconductor photocatalyst. Herein, we propose a novel and feasible strategy to incorporate dihydroxy benzene (DHB) as a conjugated monomer within the framework of urea containing CN (CNU-DHBx) to tune the electronic conductivity and charge separation due to the aromaticity of the benzene ring, which acts as an electron-donating species. Systematic characterizations such as SPV, PL, XPS, DRS, and TRPL demonstrated that the incorporation of the DHB monomer greatly enhanced the photocatalytic CO2 reduction of CN due to the enhanced charge separation and modulation of the ionic mobility. The significantly enhanced photocatalytic activity of CNU-DHB15.0 in comparison with parental CN was 85 µmol/h for CO and 19.92 µmol/h of the H2 source. It can be attributed to the electron-hole pair separation and enhance the optical adsorption due to the presence of DHB. Furthermore, this remarkable modification affected the chemical composition, bandgap, and surface area, encouraging the controlled detachment of light-produced photons and making it the ideal choice for CO2 photoreduction. Our research findings potentially offer a solution for tuning complex charge separation and catalytic reactions in photocatalysis that could practically lead to the generation of artificial photocatalysts for efficient solar energy into chemical energy conversion.
Fulltext Norfloxacin Loaded Lipid Polymer Hybrid Nanoparticles for Oral Administration: Fabrication, Characterization, In Silico Modelling and Toxicity Evaluation

Khan MA, Khan S, Kazi M, Alshehri SM, Shahid M, Khan SU, et al.

Pharmaceutics, 2021 Oct 06;13(10).
PMID: 34683925 DOI: 10.3390/pharmaceutics13101632

Norfloxacin (NOR), widely employed as an anti-bacterial drug, has poor oral bioavailability. Nano based drug delivery systems are widely used to overcome the existing oral bioavailability challenges. Lipid-Polymer Hybrid Nanoparticles (LPHNs) exhibit the distinctive advantages of both polymeric and liposomes nanoparticles, while excluding some of their disadvantages. In the current study, NOR loaded LPHNs were prepared, and were solid amorphous in nature, followed by in vitro and in vivo evaluation. The optimized process conditions resulted in LPHNs with the acceptable particle size 121.27 nm, Polydispersity Index (PDI) of 0.214 and zeta potential of -32 mv. The addition of a helper lipid, oleic acid, and polymers, ethyl cellulose, substantially increased the encapsulation efficiency (EE%) (65% to 97%). In vitro study showed a sustained drug release profile (75% within 12 h) for NOR LPHNs. The optimized NOR LPHNs showed a significant increase (p < 0.05) in bioavailability compared to the commercial product. From the acute toxicity study, the LD50 value was found to be greater than 1600 mg/kg. The molecular modelling studies substantiated the experimental results with the best combination of polymers and surfactants that produced highly stable LPHNs. Therefore, LPHNs proved to be a promising system for the delivery of NOR, as well as for other antibiotics and hydrophobic drugs.
Curcumin-laden hyaluronic acid-co-Pullulan-based biomaterials as a potential platform to synergistically enhance the diabetic wound repair

Shah SA, Sohail M, Minhas MU, Khan S, Hussain Z, Mahmood A, et al.

Int J Biol Macromol, 2021 Aug 31;185:350-368.
PMID: 34171251 DOI: 10.1016/j.ijbiomac.2021.06.119

Injectable hydrogel with multifunctional tunable properties comprising biocompatibility, anti-oxidative, anti-bacterial, and/or anti-infection are highly preferred to efficiently promote diabetic wound repair and its development remains a challenge. In this study, we report hyaluronic acid and Pullulan-based injectable hydrogel loaded with curcumin that could potentiate reepithelization, increase angiogenesis, and collagen deposition at wound microenvironment to endorse healing cascade compared to other treatment groups. The physical interaction and self-assembly of hyaluronic acid-Pullulan-grafted-pluronic F127 injectable hydrogel were confirmed using nuclear magnetic resonance (1H NMR) and Fourier transformed infrared spectroscopy (FT-IR), and cytocompatibility was confirmed by fibroblast viability assay. The CUR-laden hyaluronic acid-Pullulan-g-F127 injectable hydrogel promptly undergoes a sol-gel transition and has proved to potentiate wound healing in a streptozotocin-induced diabetic rat model by promoting 93% of wound closure compared to other groups having 35%, 38%, and 62%. The comparative in vivo study and histological examination was conducted which demonstrated an expeditious recovery rate by significantly reducing the wound healing days i.e. 35 days in a control group, 33 days in the CUR suspension group, 21 days in unloaded injectable, and 13 days was observed in CUR loaded hydrogel group. Furthermore, we suggest that the injectable hydrogel laden with CUR showed a prompt wound healing potential by increasing the cell proliferation and serves as a drug delivery platform for sustained and targeted delivery of hydrophobic moieties.
Cell membrane cloaked nanomedicines for bio-imaging and immunotherapy of cancer: Improved pharmacokinetics, cell internalization and anticancer efficacy

Hussain Z, Rahim MA, Jan N, Shah H, Rawas-Qalaji M, Khan S, et al.

J Control Release, 2021 07 10;335:130-157.
PMID: 34015400 DOI: 10.1016/j.jconrel.2021.05.018

Despite enormous advancements in the field of oncology, the innocuous and effectual treatment of various types of malignancies remained a colossal challenge. The conventional modalities such as chemotherapy, radiotherapy, and surgery have been remained the most viable options for cancer treatment, but lacking of target-specificity, optimum safety and efficacy, and pharmacokinetic disparities are their impliable shortcomings. Though, in recent decades, numerous encroachments in the field of onco-targeted drug delivery have been adapted but several limitations (i.e., short plasma half-life, early clearance by reticuloendothelial system, immunogenicity, inadequate internalization and localization into the onco-tissues, chemoresistance, and deficient therapeutic efficacy) associated with these onco-targeted delivery systems limits their clinical viability. To abolish the aforementioned inadequacies, a promising approach has been emerged in which stealthing of synthetic nanocarriers has been attained by cloaking them into the natural cell membranes. These biomimetic nanomedicines not only retain characteristics features of the synthetic nanocarriers but also inherit the cell-membrane intrinsic functionalities. In this review, we have summarized preparation methods, mechanism of cloaking, and pharmaceutical and therapeutic superiority of cell-membrane camouflaged nanomedicines in improving the bio-imaging and immunotherapy against various types of malignancies. These pliable adaptations have revolutionized the current drug delivery strategies by optimizing the plasma circulation time, improving the permeation into the cancerous microenvironment, escaping the immune evasion and rapid clearance from the systemic circulation, minimizing the immunogenicity, and enabling the cell-cell communication via cell membrane markers of biomimetic nanomedicines. Moreover, the preeminence of cell-membrane cloaked nanomedicines in improving the bio-imaging and theranostic applications, alone or in combination with phototherapy or radiotherapy, have also been pondered.
Right ureteric reconstruction with vascularised interpositional appendix graft in retroperitoneal leiomyosarcoma

Sohail M, Loke SN, Sim SK, Nik Azim NA

Med J Malaysia, 2021 05;76(3):432-435.
PMID: 34031348

We present here a case of a 66-year-old lady who was diagnosed with right iliac fossa retroperitoneal leiomyosarcoma at Hospital Umum Sarawak. The challenge in this case was the extension of tumour with the involvement of her right ureter causing proximal hydroureter and hydronephrosis. After resection of tumour en-block with the involved segment of ureter, it was not possible to repair the ureteric defect directly. We used interpositional vascularized appendix graft to repair this large (7 cm) ureteric defect. We describe here this uncommon technique of ureter reconstruction.
Fulltext Recent Advancements in Stimuli Responsive Drug Delivery Platforms for Active and Passive Cancer Targeting

Rahim MA, Jan N, Khan S, Shah H, Madni A, Khan A, et al.

Cancers (Basel), 2021 Feb 07;13(4).
PMID: 33562376 DOI: 10.3390/cancers13040670

The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.
Multi-functionalization, a Promising Adaptation to Overcome Challenges to Clinical Translation of Nanomedicines as Nano-diagnostics and Nano-therapeutics for Breast Cancer

Moti LAA, Hussain Z, Thu HE, Khan S, Sohail M, Sarfraz RM

Curr Pharm Des, 2021;27(43):4356-4375.
PMID: 34459374 DOI: 10.2174/1381612827666210830092539

BACKGROUND: Breast cancer (BC) is one of the most aggressive and prevalent types of cancer, which is associated with a high rate of mortality and colossal potential of metastasis to other body organs. Conventionally, there are three commonly employed strategies for the treatment of BC including, surgery, radiations and chemotherapy; however, these modalities are associated with several deleterious effects and a high rate of relapse.
OBJECTIVE: This review was aimed to critically discuss and conceptualize existing evidences related to the pharmaceutical significance and therapeutic feasibility of multi-functionalization of nanomedicines for early diagnosis and efficient treatment of BC.
RESULTS: Though the implication of nanotechnology-based modalities has revolutionised the outcomes of diagnosis and treatment of BC; however, the clinical translation of these nanomedicines is facing grandeur challenges. These challenges include recognition by the reticuloendothelial system (RES), short plasma half-life, non-specific accumulation in the non-cancerous cells, and expulsion of the drug(s) by the efflux pump. To circumvent these challenges, various adaptations such as PEGylation, conjugation of targeting ligand(s), and siteresponsive behaviour (i.e., pH-responsiveness, biochemical, or thermal-responsiveness) have been adapted. Similarly, multi-functionalization of nanomedicines has emerged as an exceptional strategy to improve the pharmacokinetic profile, specific targetability to the tumor microenvironment (active targeting) and efficient internalization, and to alleviate the expulsion of internalized drug contents by silencing-off efflux pump.
CONCLUSION: Critical analysis of the available evidences revealed that multi-functionalization of nanomedicines is a plausible and sustainable adaptation for early diagnosis and treatment of BC with better therapeutic outcomes.
Nano-scaled materials may induce severe neurotoxicity upon chronic exposure to brain tissues: A critical appraisal and recent updates on predisposing factors, underlying mechanism, and future prospects

Hussain Z, Thu HE, Elsayed I, Abourehab MAS, Khan S, Sohail M, et al.

J Control Release, 2020 12 10;328:873-894.
PMID: 33137366 DOI: 10.1016/j.jconrel.2020.10.053

Owing to their tremendous potential, the inference of nano-scaled materials has revolutionized many fields including the medicine and health, particularly for development of various types of targeted drug delivery devices for early prognosis and successful treatment of various diseases, including the brain disorders. Owing to their unique characteristic features, a variety of nanomaterials (particularly, ultra-fine particles (UFPs) have shown tremendous success in achieving the prognostic and therapeutic goals for early prognosis and treatment of various brain maladies such as Alzheimer's disease, Parkinson's disease, brain lymphomas, and other ailments. However, serious attention is needful due to innumerable after-effects of the nanomaterials. Despite their immense contribution in optimizing the prognostic and therapeutic modalities, biological interaction of nanomaterials with various body tissues may produce severe nanotoxicity of different organs including the heart, liver, kidney, lungs, immune system, gastro-intestinal system, skin as well as nervous system. However, in this review, we have primarily focused on nanomaterials-induced neurotoxicity of the brain. Following their translocation into different regions of the brain, nanomaterials may induce neurotoxicity through multiple mechanisms including the oxidative stress, DNA damage, lysosomal dysfunction, inflammatory cascade, apoptosis, genotoxicity, and ultimately necrosis of neuronal cells. Our findings indicated that rigorous toxicological evaluations must be carried out prior to clinical translation of nanomaterials-based formulations to avoid serious neurotoxic complications, which may further lead to develop various neuro-degenerative disorders.

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