Enhanced Anticancer Efficacy of Chemotherapy by Amphiphilic Y-Shaped Polypeptide Micelles.

Cong Hua,Yi Zhang,Yuanhao Liu

doi:10.3389/fbioe.2021.817143

Abstract

Although the treatment modalities of cancers are developing rapidly, chemotherapy is still the primary treatment strategy for most solid cancers. The progress in nanotechnology provides an opportunity to upregulate the tumor suppression efficacy and decreases the systemic toxicities. As a promising nanoplatform, the polymer micelles are fascinating nanocarriers for the encapsulation and delivery of chemotherapeutic agents. The chemical and physical properties of amphiphilic co-polymers could significantly regulate the performances of the micellar self-assembly and affect the behaviors of controlled release of drugs. Herein, two amphiphilic Y-shaped polypeptides are prepared by the ring-opening polymerization of cyclic monomer l-leucine N-carboxyanhydride (l-Leu NCA) initiated by a dual-amino-ended macroinitiator poly(ethylene glycol) [mPEG-(NH2)2]. The block co-polypeptides with PLeu8 and PLeu16 segments could form spontaneously into micelles in an aqueous solution with hydrodynamic radii of 80.0 ± 6.0 and 69.1 ± 4.8 nm, respectively. The developed doxorubicin (DOX)-loaded micelles could release the payload in a sustained pattern and inhibit the growth of xenografted human HepG2 hepatocellular carcinoma with decreased systemic toxicity. The results demonstrated the great potential of polypeptide micellar formulations in cancer therapy clinically.

Highlights

Chemotherapy is still an essential modality for the treatments of most solid cancers, a variety of emerging strategies have been developed in the past few decades (Neoptolemos et al, 2018; Bukowski et al, 2020; Lu et al, 2020; Zheng et al, 2020; Zhao et al, 2021)
The Y-shaped co-polypeptide methoxy poly(ethylene glycol) (mPEG)-(PLeu)2 was prepared by the ring-opening polymerization (ROP) of L-Leu NCA with the dual-amino-ended mPEG-(NH2)2 as a macroinitiator, as shown in Schemes 1 and 2
The successful synthesis of macroinitiator mPEG(NH2)2 and the co-polypeptide mPEG-(PLeu)2 was demonstrated through the spectrum results of 1H NMR and Fourier transform IR (FT-IR)

Summary

Introduction

Chemotherapy is still an essential modality for the treatments of most solid cancers, a variety of emerging strategies have been developed in the past few decades (Neoptolemos et al, 2018; Bukowski et al, 2020; Lu et al, 2020; Zheng et al, 2020; Zhao et al, 2021). The low water solubility, instability, short circulation period, and poor selectivity to tumor tissue of the mainstream small-molecule chemotherapeutic drugs in the clinic restrict the applicable diseases, reduce the anticancer efficacy, and even induce severe side effects (Steinbrueck et al, 2020; Zheng et al, 2021). The development of nanotechnology and the preparation of various organic and inorganic nanoparticles provide a robust tool for the controlled delivery of small-molecule chemotherapeutic drugs (Jiang et al, 2019; Sun et al, 2019; Jiang et al, 2020; Kim et al, 2020; Thomas et al, 2020; Zhang et al, 2020). The micelles self-assembled from the amphiphilic polymers are attracting increasing attention in the controlled delivery of chemotherapeutic drugs because of their controlled sizes, morphologies, stability, stimulus responsiveness, high drug loading efficiency, and targeted drug delivery behaviors (Zeinali et al, 2020; Bai et al, 2021; Rajes et al, 2021; Wei et al, 2021).

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Results

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