Precise Deposition of Polydopamine on Cancer Cell Membrane as Artificial Receptor for Targeted Drug Delivery.

Hoda Safari Yazd,Xiaowei Li,Weihong Tan,Long Li,Jianhui Jiang,Xiaoshu Pan,Yu Yang,Lu Yang,Zhuo Chen,Cheng Cui

doi:10.1016/j.isci.2020.101750

Hoda Safari Yazd, Xiaowei Li + Show 8 more

Open Access

https://doi.org/10.1016/j.isci.2020.101750

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Abstract

SummaryCompared with conventional chemotherapy and radiotherapy, targeted molecular therapy, e.g., antibody-drug conjugates or aptamer-drug conjugates, can specifically identify overexpressed natural receptors on the cancer cell, perform targeted release of anticancer drugs, and achieve targeted killing of tumor cells. However, many natural receptors are also expressed on non-cancer cells, thereby diverting the targeting molecules to healthy cells. By generating artificial cell surface receptors specific to diseased cells, aptamer-drug conjugates can identify these artificial receptors, improve therapeutic efficacy, and decrease the minimum effective dosage. In this study, we use high K+ and high H2O2 of the tumor microenvironment (TME) to produce polydopamine only on living cancer cell membrane. Owing to the significant reactivity of polydopamine with amino groups, e.g., the amino group of proteins, polydopamine can deposit on tumor cells and act as “artificial receptors” for targeted delivery of anticancer drugs with amino groups, in other words, amino-containing drugs and protein drugs.

Highlights

Current cancer therapy, such as anticancer chemotherapeutic drugs or radiation therapy, mostly cannot differentiate healthy from cancer cells owing to a lack of selectivity (Yang et al, 2016)
Owing to the significant reactivity of polydopamine with amino groups, e.g., the amino group of proteins, polydopamine can deposit on tumor cells and act as ‘‘artificial receptors’’ for targeted delivery of anticancer drugs with amino groups, in other words, amino-containing drugs and protein drugs
Traditional targeted therapy based on targeting molecules, including aptamers and antibodies, can recognize and directly bind to some specific overexpressed natural receptors on the diseased cell membrane and lead to release of anticancer drugs, achieving targeted killing of tumor cells with fewer side effects (Akhtar et al, 2014)

Summary

Introduction

Current cancer therapy, such as anticancer chemotherapeutic drugs or radiation therapy, mostly cannot differentiate healthy from cancer cells owing to a lack of selectivity (Yang et al, 2016). Targeted drug delivery can reduce drug dosage and the accompanying drug toxicity, as well as enhance therapeutic efficiency at equivalent plasma concentrations (Chari, 2008; Yang et al, 2018) To this end, several molecular targeting elements such as nucleic acid scaffolds, antibodies, and small organic molecules with recognition ability to diseased cells have been extensively investigated. Traditional targeted therapy based on targeting molecules, including aptamers and antibodies, can recognize and directly bind to some specific overexpressed natural receptors on the diseased cell membrane and lead to release of anticancer drugs, achieving targeted killing of tumor cells with fewer side effects (Akhtar et al, 2014).

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