Tumor-Microenvironment- Responsive Size-Shrinkable Drug-Delivery Nanosystems for Deepened Penetration Into Tumors.

Xiaoliang Cheng,Bo Zhao,Wei-En Yuan,Xuemei Ge,Wenwei Mao,Yao Liu,Lijuan Chen,Houli Li

doi:10.3389/fmolb.2020.576420

Abstract

Over the years, the manipulation and clinical application of drug-delivery nanosystems for cancer diseases have attracted a rapid growth of academic research interests, and some nanodrugs have been approved for clinic application. Although encouraging achievements have been made, the potency of nanomedicines in cancer treatment is far from satisfaction, and one significant reason is the inefficient penetration of nanoparticles into solid tumors. Particle size is one of the most significant features that influence diffusion ability of the drug-delivery system in tumors. Size-shrinkable drug-delivery nanosystems possess a size-switchable property that can achieve passive targeting via the enhanced permeability and retention (EPR) effect and transform into ultrasmall particles in tumors for deep penetration into tumors. The tumor microenvironment is characterized by acidic pH, hypoxia, upregulated levels of enzymes, and a redox environment. In this review, we summarize and analyze the current research progresses and challenges in tumor microenvironment responsive size-shrinkable drug-delivery nanosystems. We further expect to present some meaningful proposals and enlightenments on promoting deep penetration into tumors of nanoparticles.

Highlights

Cancer is one of many major causes for mortality worldwide
We summarize and analyze the current research progresses and challenges in the tumor microenvironment responsive size-shrinkable drug-delivery systems, especially many novel multistrategy approaches based on the tumor microenvironment response conjugated with other stimulus are discussed
We look forward that more simple size-shrinkable nanocarriers based on further basic research in tumor biology, pathology, and clinical stage are developed and translated into clinic in the recent future, and more patients benefit from nanotechnology

Summary

Introduction

Cancer is one of many major causes for mortality worldwide. Chemotherapy is a clinically practiced approach for treating cancer. Due to the biological environment of tumor tissue of relative low pH value, pH-responsible linkage could be designed and incorporated into the nanoparticle for the purpose of formulating a size-shrinkable drug-delivery system. One method for improving the targeting delivery efficiency of nanoparticles for cancer therapy is to develop nanovesicles with changeable sizes and surface characteristics, such as Zeta potential, poly(ethylene glycol) (PEG) shielding or deshielding, and conjugating of different targeting moieties to reach the desired targets.

Results

Conclusion