Effective cancer therapy based on selective drug delivery into cells across their membrane using receptor-mediated endocytosis

Bioorganic & Medicinal Chemistry Letters
Toshihiko Tashima

Abstract

Cancer is one of the major causes of death globally. The current treatment options are insufficient, leading to unmet medical needs in cancer treatment. Off-target side effects, multidrug resistance, selective distribution to cancerous tissues, and cell membrane permeation of anti-cancer agents are critical problems to overcome. There is a method to solve these problems by using receptor-mediated endocytosis (RME). It is well known that proteins such as integrin, HER2, EGFR, or other cancer biomarkers are specifically overexpressed on the surface of target cancer cells. By taking advantage of such specific receptors, payloads can be transported into cells through endocytosis using a conjugate composed of the corresponding ligands connected to the payloads by an appropriate linker. After RME, the payloads released by endosomal escape into the cytoplasm can exhibit the cytotoxic activity against cancer cells. Cell-penetrating peptides (CPPs), tumor-homing peptides (THPs), and monoclonal antibodies (mAbs) are utilized as ligands in this system. Antibody drug conjugates (ADCs) based on RME have already been used to cure cancer. In addition to the canonical conjugate method, nanocarriers for spontaneous accumulation in cancer tissue...Continue Reading

Citations

Dec 4, 2019·Current Protein & Peptide Science·Obdulia Covarrubias-ZambranoStefan H Bossmann
Jan 10, 2021·Journal of Cell Science·Krzysztof KolmusMarta Miączyńska
Feb 17, 2021·Biotechnology Advances·Pooyan MakvandiBryan Ronain Smith
Nov 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Toshihiko Tashima
Feb 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marco VeronaMattia Asti
Feb 6, 2020·Journal of Medicinal Chemistry·Chiara BorsariMaria P Costi
Apr 4, 2021·International Journal of Molecular Sciences·Toshihiko Tashima
Jun 25, 2021·Journal of Molecular Recognition : JMR·Gideon Fleminger, Avraham Dayan
Jul 26, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Liyona KampelNidal Muhanna
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Feb 19, 2019·ACS Applied Materials & Interfaces·Yi XiangWenguo Cui

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