Homotype-Targeted Biogenic Nanoparticles to Kill Multidrug-Resistant Cancer Cells

Imran Shair Mohammad,Chuchu Lin,Birendra Chaurasiya,Xuan Yang,Wei He,Hehui Rong

doi:10.3390/pharmaceutics12100950

Imran Shair Mohammad, Chuchu Lin + Show 4 more

Open Access

https://doi.org/10.3390/pharmaceutics12100950

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Abstract

“Off-targeting” and receptor density expressed at the target sites always compromise the efficacy of the nanoparticle-based drug delivery systems. In this study, we isolated different cell membranes and constructed cell membrane-cloaked biogenic nanoparticles for co-delivery of antitumor paclitaxel (PTX) and multidrug resistance (MDR)-modulator disulfiram (DSF). Consequently, MDR cancer cell membrane (A549/T)-coated hybrid nanoparticles (A549/T CM-HNPs) selectively recognized the source cells and increased the uptake by ninefold via the homotypic binding mechanism. Moreover, the A549/T CM-HNPs sensitized MDR cells to PTX by suppressing P-glycoprotein (P-gp) activity by 3.2-fold and induced effective apoptosis (70%) in homologous A549/T cells. Cell-membrane coating based on the “homotypic binding” is promising in terms of promoting the accumulation of chemotherapeutics in MDR cells and killing them.

Highlights

Cancer is a leading cause of death worldwide, due to the multiple carcinogenic processes entailed with various incomprehensible and complex cellular pathways [1,2]
The preparation of CM-hybrid nanoparticles (HNPs) was accomplished in three major steps, (1) synthesis of Cationic BSA (CBSA); (2) preparation of red blood cells (RBCs), LO2, 4T1, and A549/T CM vesicles; and (3) cell membrane cloaking of CBSA-HNP cores
The CBSA was synthesized from native bovine from serumnative albumin (BSA) through ethylenediamine modification by amide linkages, and zeta potential measurement of BSA and CBSA showed −21 mV and +17 mV, respectively

Summary

Introduction

Cancer is a leading cause of death worldwide, due to the multiple carcinogenic processes entailed with various incomprehensible and complex cellular pathways [1,2]. Despite the advancement in conventional cancer treatments (chemotherapy, radiation, or surgery), cancer therapy is still hampered by poor specificity, inadequate drug distribution, and serious systemic toxicities [3]. Nanoparticle-mediated drug delivery system (NDDS) improves drug accumulation in tumors and allows for enhanced antitumor efficacy. “off-targeting” and receptor density expressed at the target sites always compromise the efficacy of the NDDS. In order to accurately target tumor cells, various bio-mimetic strategies were explored to deliver payload at intended sites [4,5]. Coating nanoparticles (NPs) with source cell membrane-derived from the homologous tumor enabled NP self-recognition, enhancing internalization and efficient tumor homing to the homologous tumors [6]

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