The merger of nanotechnology and combination chemotherapy has shown notable promise in the therapy of resistant tumors. The latest scientific attention encompasses the engagement of anticancer drugs in combination with small interfering (si)RNAs, such as VEGF, XLAP, PGP, MRP-1, BCL-2 and cMyc, to name but a few. siRNAs have shown immense promise to knockout drug resistance genes as well as to recover the sensitivity of resistant tumors to anticancer therapy. The nanotechnology approach could also protect siRNA against RNAse degradation as well as prevent off-target effects. In this article, we discuss the approaches that have been used to deliver of siRNA in combination with chemotherapeutic drugs to treat resistant tumors. We also discuss the stipulations that must be considered in formulating a nanotechnology-assisted siRNA-drug cancer therapy.
Galactosylated nanocarriers have recently emerged as viable and versatile tools to deliver drugs at an optimal rate specifically to their target tissues or cells, thus maximizing their therapeutic benefits while circumventing off-target effects. The abundance of lectin receptors on cell surfaces makes the galactosylated carriers suitable for the targeted delivery of bioactives. Additionally, tethering of galactose (GAL) to various carriers, including micelles, liposomes, and nanoparticles (NPs), might also be appropriate for drug delivery. Here, we review recent advances in the development of galactosylated nanocarriers for active tumor targeting. We also provide a brief overview of the targeting mechanisms and cell receptor theory involved in the ligand-receptor-mediated delivery of drug carriers.
The cluster-determinant 44 (CD44) receptor has a high affinity for hyaluronic acid (HA) binding and is a desirable receptor for active targeting based on its overexpression in cancer cells compared with normal body cells. The nanocarrier affinity can be increased by conjugating drug-loaded carriers with HA, allowing enhanced cancer cell uptake via the HA-CD44 receptor-mediated endocytosis pathway. In this review, we discuss recent advances in HA-based nanocarriers and micelles for cancer therapy. In vitro and in vivo experiments have repeatedly indicated HA-based nanocarriers to be a target-specific drug and gene delivery platform with great promise for future applications in clinical cancer therapy.
A tumor serves as a major avenue in drug development owing to its complexity. Conventional therapies against tumors possess limitations such as suboptimal therapeutic efficacy and extreme side effects. These display poor pharmacokinetics and lack specific targeting, with non-specific distribution resulting in systemic toxicity. Therefore, nanocarriers targeted against cancers are increasingly being explored. Nanomedicine aids in maintaining a balance between efficacy and toxicity by specifically accumulating in tumors. Nanotherapeutics possess advantages such as increased solubility of chemotherapeutics, encapsulation of multiple drugs and improved biodistribution, and can ensure tumor-directed drug delivery and release via the approaches of passive targeting and active targeting. This review aims to offer a general overview of the current advances in tumor-targeting nanocarriers for clinical and diagnostic use.
Aging is one of the major risk factors for most neurodegenerative disorders including Parkinson's disease (PD). More than 10 million people are affected with PD worldwide. One of the predominant factors accountable for progression of PD pathology could be enhanced accumulation of senescent cells in the brain with the progress of age. Recent investigations have highlighted that senescent cells can ignite PD pathology via increased oxidative stress and neuroinflammation. Senolytics are agents that kill senescent cells. This review mainly focuses on understanding the pathological connection between senescence and PD, with emphasis on some of the recent advances made in the area of senolytics and their evolution to potential clinical candidates for future pharmaceuticals against PD.
Mesenchymal stem cells (MSCs) are susceptible to replicative senescence and senescence-associated functional decline, which hampers their use in regenerative medicine. Senotherapeutics are drugs that target cellular senescence through senolytic and senomorphic functions to induce apoptosis and suppress chronic inflammation caused by the senescence-associated secreted phenotype (SASP), respectively. Therefore, senotherapeutics could delay aging-associated degeneration. They could also be used to eliminate senescent MSCs during in vitro expansion or bioprocessing for transplantation. In this review, we discuss the role of senotherapeutics in MSC senescence, rejuvenation, and transplantation, with examples of some tested compounds in vitro. The prospects, challenges, and the way forward in clinical applications of senotherapeutics in cell-based therapeutics are also discussed.
Resistance of cancer cells to anticancer drugs is the main reason for the failure of traditional cancer treatments. Various cellular components and different loops within the signaling pathways contribute to drug resistance which could be modulated with the aim to restore drug efficacy. Unveiling the molecular mechanisms for cancer drug resistance has now paved the way for the development of novel approaches to regulate the response rates to anticancer drugs at the genetic level. The recent progress on identification and validation of the vital genes directly or indirectly involved in development of cancer drug resistance with the aid of the specific knock down ability of RNA interference technology is discussed in this review.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons. Motor features such as tremor, rigidity, bradykinesia and postural instability are common traits of PD. Current treatment options provide symptomatic relief to the condition but are unable to reverse disease progression. The conventional single-target therapeutic approach might not always induce the desired effect owing to the multifactorial nature of PD. Hence, multitarget strategies have been proposed to simultaneously target multiple proteins involved in the development of PD. Herein, we provide an overview of the pathogenesis of PD and the current pharmacotherapies. Furthermore, rationales and examples of multitarget approaches that have been tested in preclinical trials for the treatment of PD are also discussed.
The successful regulatory authority approval rate of drug candidates in the drug development pipeline is crucial for determining pharmaceutical research and development (R&D) efficiency. Regulatory authorities include the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Pharmaceutical and Food Safety Bureau Japan (PFSB), among others. Optimal drug metabolism and pharmacokinetics (DMPK) properties influence the progression of a drug candidate from the preclinical to the clinical phase. In this review, we provide a comprehensive assessment of essential concepts, methods, improvements, and challenges in DMPK science and its significance in drug development. This information provides insights into the association of DMPK science with pharmaceutical R&D efficiency.
Maintenance of oral health is a major challenge in dentistry. Different materials have been used to treat various dental diseases, although treatment success is limited by features of the biomaterials used. To overcome these limitations, materials incorporated with nanoparticles (NPs) can be used in dental applications including endodontics, periodontics, tissue engineering, oral surgery, and imaging. The unique properties of NPs, including their surface:volume ratio, antibacterial action, physical, mechanical, and biological characteristics, and unique particle size have rendered them effective vehicles for dental applications. In this review, we provide insights into the various applications of NPs in dentistry, including their benefits, limitations, properties, actions and future potential.
To avoid tissue rejection during organ transplantation, research has focused on the use of tissue engineering to regenerate required tissues or organs for patients. The biomedical applications of hyperbranched, multivalent, structurally uniform, biocompatible dendrimers in tissue engineering include the mimicking of natural extracellular matrices (ECMs) in the 3D microenvironment. Dendrimers are unimolecular architects that can incorporate a variety of biological and/or chemical substances in a 3D architecture to actively support the scaffold microenvironment during cell growth. Here, we review the use of dendritic delivery systems in tissue engineering. We discuss the available literature, highlighting the 3D architecture and preparation of these nanoscaffolds, and also review challenges to, and advances in, the use dendrimers in tissue engineering. Advances in the manufacturing of dendritic nanoparticles and scaffold architectures have resulted in the successful incorporation of dendritic scaffolds in tissue engineering.
Theranostics has the potential to revolutionize the diagnosis, treatment, and prognosis of cancer, where novel drug delivery systems could be used to detect the disease at an early stage with instantaneous treatment. Various preclinical approaches of nanoemulsions with entrapped contrast and chemotherapeutic agents have been documented to act specifically on the tumor microenvironment (TME) for both diagnostic and therapeutic purposes. However, bringing these theranostic nanoemulsions through preclinical trials to patients requires several fundamental hurdles to be overcome, including the in vivo behavior of the delivery tool, degradation, and clearance from the system, as well as long-term toxicities. Here, we discuss recent advances in the application of nanoemulsions in molecular imaging with simultaneous therapeutic efficacy in a single delivery system.