CD44-Receptors-Mediated Multiprong Targeting Strategy Against Breast Cancer and Tumor-Associated Macrophages: Design, Optimization, Characterization, and Cytologic Evaluation.

IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY
International Journal of Nanomedicine Pub Date : 2025-01-25 eCollection Date: 2025-01-01 DOI:10.2147/IJN.S480553
Zahid Hussain, Lama Abdulrahim Abdul Moti, Jayalakshmi Jagal, Hnin Ei Thu, Shahzeb Khan, Mohsin Kazi
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引用次数: 0

Abstract

Introduction: Owing to its high prevalence, colossal potential of chemoresistance, metastasis, and relapse, breast cancer (BC) is the second leading cause of cancer-related fatalities in women. Several treatments (eg, chemotherapy, surgery, radiations, hormonal therapy, etc.) are conventionally prescribed for the treatment of BC; however, these are associated with serious systemic aftermaths. In this research, we aimed to design a multiprong targeting strategy for concurrent action against different phenotypes of BC (MCF-7 and SK-BR-3) and tumor-associated macrophages (TAMs) for relapse-free treatment of BC.

Methods: Paclitaxel (PTX) and tamoxifen (TMX) co-loaded chitosan (CS) nanoparticles (NPs) were prepared using the ionic-gelation method and optimized using the Design Expert® software by controlling different material attributes. For selective targeting through CD44-receptors that are heavily expressed on the BC cells and TAMs, the fabricated NPs (PTX-TMX-CS-NPs) were functionalized with hyaluronic acid (HA) as a targeting ligand.

Results: The optimized HA-PTX-TMX-CS-NPs exhibited desired physicochemical properties (PS ~230 nm, PDI 0.30, zeta potential ~21.5 mV), smooth spherical morphology, high encapsulation efficiency (PTX ~72% and TMX ~97%), good colloidal stability, and biphasic release kinetics. Moreover, the lowest cell viability depicted in MCF-7 (~25%), SK-BR-3 (~20%), and RAW 264.7 cells (~20%), induction of apoptosis, cell cycle arrest, enhanced cell internalization, and alleviation of MCF-7 and SK-BR-3 migration proved the superior anticancer potential of HA-PTX-TMX-CS-NPs compared to unfunctionalized NPs and other control medicines.

Conclusion: HA-functionalization of NPs is a promising multiprong strategy for CD44-receptors-mediated targeting of BC cells and TAMs to mitigate the progression, metastasis, and relapse in the BC.

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来源期刊
International Journal of Nanomedicine
International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY
CiteScore
14.40
自引率
3.80%
发文量
511
审稿时长
1.4 months
期刊介绍: The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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