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A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies
Published on: November 7, 2015
Tumor Microenvironment Targeted Nanotherapy
Clara Fernandes1, Divya Suares1, Mayur C Yergeri1
1Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's Narsee Monjee Institute of Management Studies - NMIMS, Mumbai, India.
Abstract:
Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. While enhanced permeability and retention effect promotes nano-chemotherapeutics extravasation, the abnormal tumor vasculature, high interstitial pressure and dense stroma structure limit homogeneous intratumoral distribution of nano-chemotherapeutics and compromise their imaging and therapeutic effect. Moreover, heterogeneous distribution of nano-chemotherapeutics in non-tumor-stroma cells damages the non-tumor cells, and interferes with tumor-stroma crosstalk. This can lead not only to inhibition of tumor progression, but can also paradoxically induce acquired resistance and facilitate tumor cell proliferation and metastasis. Overall, the tumor microenvironment plays a vital role in regulating nano-chemotherapeutics distribution and their biological effects. In this review, the barriers in tumor microenvironment, its consequential effects on nano-chemotherapeutics, considerations to improve nano-chemotherapeutics delivery and combinatory strategies to overcome acquired resistance induced by tumor microenvironment have been summarized. The various strategies viz., nanotechnology based approach as well as ligand-mediated, redox-responsive, and enzyme-mediated based combinatorial nanoapproaches have been discussed in this review.
Insights
Nanotechnology offers new cancer treatments, but the tumor microenvironment hinders drug delivery. Strategies are reviewed to improve distribution and overcome drug resistance for better cancer therapy.
Area of Science:
- Oncology
- Nanotechnology
- Biomedical Engineering
Background:
- Nanotechnology advances offer novel cancer diagnosis and therapy approaches.
- The enhanced permeability and retention (EPR) effect aids nano-chemotherapeutics extravasation.
- However, tumor microenvironment barriers impede homogeneous intratumoral distribution and efficacy.
Purpose of the Study:
- To review tumor microenvironment barriers affecting nano-chemotherapeutics.
- To summarize strategies for improving nano-chemotherapeutics delivery.
- To discuss combinatorial approaches for overcoming acquired resistance.
Main Methods:
- Review of existing literature on nanotechnology in cancer therapy.
- Analysis of tumor microenvironment factors influencing nanoparticle distribution.
- Exploration of various nanotechnology-based and combinatorial strategies.
Main Results:
- Tumor vasculature, interstitial pressure, and stroma limit drug distribution and efficacy.
- Heterogeneous distribution can damage non-tumor cells and induce acquired resistance.
- Combinatorial strategies involving nanotechnology, ligand-mediated, redox-responsive, and enzyme-mediated approaches show promise.
Conclusions:
- The tumor microenvironment critically regulates nano-chemotherapeutics distribution and effects.
- Overcoming these barriers is essential for effective cancer nanomedicine.
- Targeted delivery and combination therapies are key to enhancing therapeutic outcomes.
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