M2 macrophage microvesicle-inspired nanovehicles improve accessibility to cancer cells and cancer stem cells in tumors

Yuqi Wang,Xiaoxuan Xu,Xiang Gong,Zhiwen Zhang,Yaping Li,Yao Wu,Jie Li,Siling Wang,Jiaoying Wang,Hong Wang

doi:10.1186/s12951-021-01143-5

Abstract

Cancer cells and cancer stem cells (CSCs) are the major players of cancer malignancy and metastasis, but they are extremely difficult to access. Inspired by the vital role of macrophages and microvesicle-mediated cell–cell communication in tumors, we herein designed M2 macrophage microvesicle-inspired nanovehicle of cabazitaxel (M-CFN) to promote accessibility to cancer cells and CSCs in tumors. In the 4T1 tumor model, M-CFN flexibly permeated the tumor mass, accessed cancer cells and CD90-positive cells, and significantly promoted their entry into CSC fractions in tumors. Moreover, M-CFN treatment profoundly eliminated aldehyde dehydrogenase (ALDH)-expressing CSCs in 4T1 and MCF-7 tumors, produced notable depression of tumor growth and caused 93.86% suppression of lung metastasis in 4T1 models. Therefore, the M2 macrophage microvesicle-inspired nanovehicle provides an encouraging strategy to penetrate the tumor tissues and access these insult cells in tumors for effective cancer therapy.Graphical

Highlights

Cancer cells and cancer stem cells (CSCs) are the major players that orchestrate cancer malignancy and metastasis in many types of solid tumors [1, 2]
Preparation and characterizations of M‐cabazitaxel-loaded polyfluorocarbon nanoparticles (CFN) Initially, M2 macrophage microvesicle-inspired nanovehicle of cabazitaxel (M-CFN) was fabricated in two steps: (1) preparing CFN with CTX and amphiphilic polyfluorocarbon polymeric materials (PFP) and poly(ε-caprolactone)block-poly(ethylene glycol) (PCL-PEG); (2) inducing M2 macrophages from murine RAW264.7 cells and isolating M2 macrophage membranes to camouflage CFN via an extrusion method to form M-CFN
Western blotting analysis indicated that typical markers of macrophages, including CD11b, colony stimulating factor 1 receptor (CSF1R), β1-integrins, α4-integrins and C–C motif chemokine receptor 2 (CCR2), were readily detected in the macrophage derived microvesicles, MM and M-CFN, but were undetectable in their counterpart CFN (Fig. 1F)

Summary

Introduction

Cancer cells and cancer stem cells (CSCs) are the major players that orchestrate cancer malignancy and metastasis in many types of solid tumors [1, 2]. CSCs can transform into rapidly dividing cancer cells to foster tumor progression, and cancer cells can evolve into CSCs to protect themselves from therapeutic intervention. Some commonly used anticancer drugs, such as paclitaxel, cisplatin, and sunitinib, efficiently damage rapidly dividing cancer cells [1, 8, 9], but they are ineffective in eliminating CSCs; worse still, they may unexpectedly enrich the ratio of CSCs in tumors [9,10,11]. Cancer cells and CSCs are frequently embedded in the dense tumor stroma comprising versatile stromal cells and extracellular matrix networks, making them extremely difficult access [5, 20, 21]. Therapeutic agents should be delivered across the tumor stroma barriers and access cancer cells and CSCs to exert anticancer effects [22, 23]. It is impressively desired to develop novel delivery strategies to improve their accessibility to these insult cells for cancer therapy

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Results

Conclusion