Exploring the Potential of Nanotherapeutics in Targeting Tumor Microenvironment for Cancer Therapy

Muntimadugu, Eameema; Kommineni, Nagavendra; Khan, Wahid

doi:10.1016/j.phrs.2017.05.010

Cited by 65 publications

(46 citation statements)

References 146 publications

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“…Matsumura and Maeda ( 1986 ) were the first to demonstrate the phenomenon of EPR effect of macromolecules in tumor, ascribed to leaky tumor vasculature (Figure 3 ). Preclinically, ten times higher localization was reported for nanoparticles in the particle size range of 10–100 nm in diameter (Miao and Huang, 2015 ; Muntimadugu et al, 2017 ). However, in clinical setting, owing to the complex and heterogenous nature of human tumors, intra-/inter- variability in both tumor characteristics and tumor microenvironment in patient populations, EPR based paradigm approach failed to replicate the success of preclinical studies (Bjrnmalm et al, 2017 ).…”

Section: Understanding the Challenges And Opportunities Presented By mentioning

confidence: 92%

Tumor Microenvironment Targeted Nanotherapy

2018

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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.

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Section: Understanding the Challenges And Opportunities Presented By mentioning

confidence: 92%

Tumor Microenvironment Targeted Nanotherapy

2018

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“…Recently, it has been reported that current animal models fail to predict the accumulation of nanocarriers inside the tumor, which is actually about 0.7% of the injected dose [ 172 , 173 ]. Thus, animal models that would allow us to better study the ability of nanocarriers in this step are crucial to ensuring an effective therapeutic effect [ 174 ]. The complexity of the tumor extracellular matrix (ECM) may also restrict the extravasation of the nanocarriers.…”

Section: The Potential Of Zebrafish For Increasing the Translationmentioning

confidence: 99%

The Potential of Zebrafish as a Model Organism for Improving the Translation of Genetic Anticancer Nanomedicines

Gutiérrez-Lovera

Vázquez-Ríos

Guerra‐Varela

et al. 2017

Genes

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In the last few decades, the field of nanomedicine applied to cancer has revolutionized cancer treatment: several nanoformulations have already reached the market and are routinely being used in the clinical practice. In the case of genetic nanomedicines, i.e., designed to deliver gene therapies to cancer cells for therapeutic purposes, advances have been less impressive. This is because of the many barriers that limit the access of the therapeutic nucleic acids to their target site, and the lack of models that would allow for an improvement in the understanding of how nanocarriers can be tailored to overcome them. Zebrafish has important advantages as a model species for the study of anticancer therapies, and have a lot to offer regarding the rational development of efficient delivery of genetic nanomedicines, and hence increasing the chances of their successful translation. This review aims to provide an overview of the recent advances in the development of genetic anticancer nanomedicines, and of the zebrafish models that stand as promising tools to shed light on their mechanisms of action and overall potential in oncology.

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“…Therefore, changing the cancer microenvironment is on track to become a new strategy for tumour immunotherapy, and much research has focussed on therapeutic protocols against TME elements, such as combined therapies and nanomedicines [37][38][39]. Previous studies have shown that immunotherapy for cancer micrometastases employing an IL-21-based cellular vaccine can be significantly augmented through CD25þ regulatory T cell depletion [40], and a combination of vaccination with agents that disarm TGFb would enhance the vaccine's efficacy [41].…”

Section: Discussionmentioning

confidence: 99%

Anti-tumour effects of a xenogeneic fibroblast activation protein-based whole cell tumour vaccine in murine tumour models

Chen

Fan

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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The clinical benefit of cancer immunotherapy, including tumour vaccines, is influenced by immunosuppressive factors in the tumour microenvironment. Among these factors, cancer-associated fibroblasts (CAFs) and their products, such as fibroblast activation protein-a (FAPa), greatly affect tumourigenesis, development, metastasis and treatment tolerance, which make them promising immunotherapy targets for cancer patients. Our previous study reported that a whole cell tumour vaccine (WCTV) expressing FAPa inhibited tumour growth by simultaneously attacking cancer cells and CAFs. This study aimed to improve WCTVs with xenoantigens to end immune tolerance and to further activate the adaptive immune system. In the present study, we designed a WCTV by transducing a vector encoding human FAPa (hFAPa) into murine tumour cells and evaluated its efficacy in multiple solid tumour models. Immunotherapy with this WCTV effectively delayed tumour growth and prevented recurrence. The anti-tumour responses were clearly linked to antigen-specific cytotoxic T cells, whereas CD4(þ) T lymphocytes also played a role. Humoural immune responses were activated because the adoptive transfer of immunoglobulins induced abscopal anti-tumour effects, and autoantibodies against FAPa were specifically detected in the sera of immunized mice. Moreover, an increased number of apoptotic tumour cells along with a reduced number of CAFs within the tumours suggest that xenogeneic FAPa-based WCTV has the potential to drive T cell and antibody responses against cancer cells and CAFs. This finding could offer an advanced strategy to treat multiple solid tumours with individualized cancer immunotherapy techniques.

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Exploring the Potential of Nanotherapeutics in Targeting Tumor Microenvironment for Cancer Therapy

Cited by 65 publications

References 146 publications

Tumor Microenvironment Targeted Nanotherapy

Tumor Microenvironment Targeted Nanotherapy

The Potential of Zebrafish as a Model Organism for Improving the Translation of Genetic Anticancer Nanomedicines

Anti-tumour effects of a xenogeneic fibroblast activation protein-based whole cell tumour vaccine in murine tumour models

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