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Breaking the niche: multidimensional nanotherapeutics for tumor microenvironment modulation

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Abstract

Most of the current antitumor therapeutics were developed targeting the cancer cells only. Unfortunately, in the majority of tumors, this single-dimensional therapy is found to be ineffective. Advanced research has shown that cancer is a multicellular disorder. The tumor microenvironment (TME), which is made by a complex network of the bulk tumor cells and other supporting cells, plays a crucial role in tumor progression. Understanding the importance of the TME in tumor growth, different treatment modalities have been developed targeting these supporting cells. Recent clinical results suggest that simultaneously targeting multiple components of the tumor ecosystem with drug combinations can be highly effective. This type of “multidimensional” therapy has a high potential for cancer treatment. However, tumor-specific delivery of such multi-drug combinations remains a challenge. Nanomedicine could be utilized for the tumor-targeted delivery of such multidimensional therapeutics. In this review, we first give a brief overview of the major components of TME. We then highlight the latest developments in nanoparticle-based combination therapies, where one drug targets cancer cells and other drug targets tumor-supporting components in the TME for a synergistic effect. We include the latest preclinical and clinical studies and discuss innovative nanoparticle-mediated targeting strategies.

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SDL and AR acknowledge funding support from Shastri Indo-Canadian Institute.

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Authors and Affiliations

  1. Department of Pharmacy, Birla Institute of Technology & Science, Vidya Vihar, Pilani, Rajasthan, 333031, India

    K. Laxmi Swetha, Kavya Sree Maravajjala & Aniruddha Roy

  2. Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Westbrook Mall, Vancouver, BC, Canada

    Shyh-Dar Li

  3. Department of Biotechnology, Bennett University, Greater Noida, Uttar Pradesh, 201310, India

    Manu Smriti Singh

  4. Center of Excellence for Nanosensors and Nanomedicine, Bennett University, Greater Noida, Uttar Pradesh, 201310, India

    Manu Smriti Singh

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Karnam Laxmi Swetha: Conceptualization; formal analysis; investigation; methodology; writing—original draft. Kavya Sree Maravajjala: Data curation; methodology; writing—original draft. Shyh-Dar Li: Funding acquisition; writing—review and editing. Manu Smriti Singh: Conceptualization; formal analysis; writing, original draft; writing, review and editing. Aniruddha Roy: Conceptualization; supervision; formal analysis; funding acquisition; writing, original draft, writing, review and editing.

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Swetha, K.L., Maravajjala, K.S., Li, SD. et al. Breaking the niche: multidimensional nanotherapeutics for tumor microenvironment modulation. Drug Deliv. and Transl. Res. 13, 105–134 (2023). https://doi.org/10.1007/s13346-022-01194-7

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