Tumor‐Targeting Glycol Chitosan Nanoparticles for Cancer Heterogeneity

Abstract

liposomes (Doxil; liposomal doxorubicin (DOX), Onivyde; liposomal irinotecan, Vyxeos; liposomal daunorubicin plus cytarabine) and albumin nanoparticles (Abraxane; albumin nanoparticle-bound paclitaxel), being approved for clinical use and other nanocarriers being at different stages of clinical development. [2] Despite recent research and development of nanomedicines, the success rate of clinical translation remains poor, with patients in clinical settings benefitting from nanomedicines only through a reduction in side effects. [3] This is primarily because the enhanced accumulation of nanoparticles at tumor sites was initially overvalued in preclinical settings, with insufficient consideration given to tumor heterogeneity and complexity. [4] An analysis of studies published from 2005 to 2015 on the efficiency of nanoparticle delivery found that only 0.7% of the administered dose of nanoparticles was delivered to the tumor, irrespective of the materials, targeting strategy, hydrodynamic diameter, zeta potential, shape of nanoparticles, tumor model, and cancer type. [5] This low efficiency of delivery has prompted investigations to determine whether any key factors were omitted in the design and development of nanocarriers. A fundamental understanding of the key factors determining the tumor-targeting ability of nanoparticles is therefore required to optimize the design and development of nanoparticles with enhanced efficiency of delivery to tumors. Although many studies have assessed the impact of nanocarrier properties on the efficiency of targeted delivery, the effects of different factors are interconnected and often in opposition. For example, coating the surfaces of nanocarriers with poly(ethylene glycol) (PEG) extends their circulation in the blood by minimizing their detection by the immune system, thus contributing to targeted accumulation. However, PEG also reduces the uptake of nanocarriers by tumor tissue or tumor cells, reducing the accumulation of nanocarriers in tumors. Therefore, integrated analysis of the key factors found in a single type of nanoparticle with excellent tumor-targeting ability may provide insights into the entire procedure of developing new tumor-targeting nanocarriers. The relatively moderate therapeutic efficacy of nanomedicines in clinical settings may be due in part to tissue heterogeneity. The clinical benefits of nanomedicines have been reported to be highly variable and limited compared with their Nanomedicine is extensively employed for cancer treatment owing to its unique advantages over conventional drugs and imaging agents. This increased attention to nanomedicine, however, has not fully translated into clinical utilization and patient benefits due to issues associated with reticuloendothelial system clearance, tumor heterogeneity, and complexity of the tumor microenvironment. To address these challenges, efforts are being made to modify the design of nanomedicines, including optimization of their physiochemical properties, active targeting, and response to stimuli, but...

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