Healthcare providers experience moral injury when their internal ethics are violated. The routine and direct exposure to ethical violations makes clinicians vulnerable to harm. The fundamental ethics in health care typically fall into the four broad categories of patient autonomy, beneficence, nonmaleficence, and social justice. Patients have a moral right to determine their own goals of medical care, that is, they have autonomy. When this principle is violated, moral injury occurs. Beneficence is the desire to help people, so when the delivery of proper medical care is obstructed for any reason, moral injury is the result. Nonmaleficence, meaning do no harm, has been a primary principle of medical ethics throughout recorded history. Yet today, even the most advanced and safest medical treatments are associated with unavoidable, harmful side effects. When an inevitable side effect occurs, the patient is harmed, and the clinician is also at risk of moral injury. Social injustice results when patients experience suboptimal treatment due to their race, gender, religion, or other demographic variables. While minor ethical dilemmas and violations routinely occur in medical care and cannot be eliminated, clinicians can decrease the prevalence of a significant moral injury by advocating for the ethical treatment of patients, not only at the bedside but also by addressing the ethics of political influence, governmental mandates, and administrative burdens on the delivery of optimal medical care. Although clinicians can strengthen their resistance to moral injury by deepening their own spiritual foundation, that is not enough. Improvements in the ethics of the entire healthcare system are necessary to improve medical care and decrease moral injury.
Polyethylenimine (PEI) is one of the most broadly used polycations for gene delivery due to its high transfection efficiency and commercial availability but materials are cytotoxic and often polydisperse. The goal of current work is to develop an alternative family of polycations based on controlled living radical polymerization (CLRP) and to optimize the polymer structure for efficient gene delivery. In this study, well-defined poly(glycidyl methacrylate)(P(GMA)) homopolymers were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization followed by decoration using three different types of oligoamines, i.e., tetraethylenepentamine (TEPA), pentaethylenehexamine (PEHA), and tris(2-aminoethyl)amine (TREN), respectively, to generate various P(GMA-oligoamine) homopolycations. The effect of P(GMA) backbone length and structure of oligoamine on gene transfer efficiency was then determined. The optimal polymer, P(GMA-TEPA)(50), provided comparable transfection efficiency but lower cytotoxicity than PEI. P(GMA-TEPA)(50) was then used as the cationic block in diblock copolymers containing hydrophilic N-(2-hydroxypropyl) methacrylamide (HPMA) and oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA). Polyplexes of block copolymers were stable against aggregation in physiological salt condition and in Opti-MEM due to the shielding effect of P(HPMA) and P(OEGMA). However, the presence of the HPMA/OEGMA block significantly decreased the transfection efficacy of P(GMA-TEPA)(50) homopolycation. To compensate for reduced cell uptake caused by the hydrophilic shell of polyplex, the integrin-binding peptide, RGD, was conjugated to the hydrophilic chain end of P(OEGMA)(15)-b-P(GMA-TEPA)(50) copolymer by Michael-type addition reaction. At low polymer to DNA ratios, the RGD-functionalized polymer showed increased gene delivery efficiency to HeLa cells compared to analogous polymers lacking RGD.