Nanocarriers for delivering nucleic acids and chemotherapeutic agents as combinational approach: Challenges, clinical progress, and unmet needs

Cancer is the second leading cause of death after heart disease. It forms clusters of immature cells, spreads through metastasis, and invades normal tissue. Chemotherapeutic approaches for cancer can have negative impacts, such as chronic toxicity and chemoresistance, and result in treatment failure, ultimately challenging clinical cancer therapeutics. Gene modulatory approaches have been adopted to reestablish anticancer drug efficacy as research into the genetic variations involved in chemoresistance acquisition has progressed. Many intelligent nanocarriers have been developed and fine-tuned to facilitate the combinational therapy of nucleic acids and anticancer drugs. This review attempts to determine a rational design of nanocarrier-loaded genes and anticancer drugs with the goal of chemoresistance reversal at various cellular levels. This review discusses the fundamentals of therapeutic loading, tuning of physicochemical characteristics, and various modifications to nanocarriers. In addition, this review explores the recent advancements and clinical progress that have been addressed and are expected to produce outstanding results in the near future.