Responsive Role of Nanomedicine in the Tumor Microenvironment and Cancer Drug Resistance

Abstract

Cancer remains a major worldwide health challenge. Current studies emphasize the tumor microenvironment that plays a vital role in tumor proliferation, invasion, metastasis, and drug resistance. The tumor microenvironment supports the cancer cell to evade conventional treatment such as surgery, radiotherapy, and chemotherapy. Moreover, the components of tumor microenvironments have a major contribution to developing therapy resistance in solid tumors. Therefore, targeting the tumor microenvironment can be a novel approach to achieving advancement in cancer nanomedicine. The recent progress in understanding TME and developing TME-responsive nanoparticles offers a great advantage in treating cancer drug resistance. These nanoparticles developed in response to TME stimuli such as low pH, redox, and hypoxia improve nanomedicine's pharmacokinetic and therapeutic efficacy. This review discusses the various components of the tumor microenvironment responsible for drug resistance and nanomedicine's role in overcoming it.

Supramolecular host-guest nanosystems for overcoming cancer drug resistance

“…The acidic tumor microenvironment commonly found in solid tumors can reduce the endocytosis of free drugs and dissociate drug molecules [69,70] . Therefore, pH-responsive supramolecular host-guest nanosystems have been widely developed to enhance cell internalization and protect drugs from dissociation [71][72][73] . He et al prepared a pH-responsive nanoparticle (Ac-α-CD NP) based on acetylated α-CD (Ac-α-CD), which permission from Shi et al [75] .…”

Evolving Tumor Characteristics and Smart Nanodrugs for Tumor Immunotherapy

“…6,10 However, the effectiveness of microenvironment-responsive nanodrugs in tumor therapy is limited by the tumor cell evolution, which can lead to mutations that alter receptor expression, thereby diminishing the therapeutic effect of these nanodrugs and contributing to TME heterogeneity. 11 The complexity of the TME varies not only across different types of tumors but also within the same tumor, affecting the efficacy of certain nanodrugs. 12 Moreover, the presence of multiple drugresistant proteins expressed by cells within the TME can further reduce the effectiveness of responsive nanodrugs.…”

Phytochemical-Based Nanomedicine for Targeting Tumor Microenvironment and Inhibiting Cancer Chemoresistance: Recent Advances and Pharmacological Insights

“…12 However, the development of multidrug resistance (MDR) is a significant clinical challenge, where the components of TME are major contributors to drug resistance in solid tumors. 13 For example activation of CXCL5/PI3K/AKT/mTOR pathway in tumor-associated macrophages (TAMs) enhanced the chemoresistance of gastric cancer. 14 Moreover, the activation of NF-kB, IL6/STAT3, ERK/MAPK, and YAP/TAZ signaling promotes crosstalk between TME and tumor cells resulting in chemoresistance.…”

“…Consequently, combination therapy (conventional and CSC-targeted therapy) shows favorable outcomes for the elimination of cancer . However, the development of multidrug resistance (MDR) is a significant clinical challenge, where the components of TME are major contributors to drug resistance in solid tumors . For example activation of CXCL5/PI3K/AKT/mTOR pathway in tumor-associated macrophages (TAMs) enhanced the chemoresistance of gastric cancer .…”