Engineered Mesenchymal Stem Cell/Nanomedicine Spheroid as an Active Drug Delivery Platform for Combinational Glioblastoma Therapy

Abstract

Mesenchymal stem cell (MSC) has been increasingly applied to cancer therapy because of its tumor-tropic capability. However, short retention at target tissue and limited payload option hinder the progress of MSC-based cancer therapy. Herein, we proposed a hybrid spheroid/nanomedicine system, comprising MSC spheroid entrapping drug-loaded nanocomposite, to address these limitations. Spheroid formulation enhanced MSC’s tumor tropism and facilitated loading of different types of therapeutic payloads. This system acted as an active drug delivery platform seeking and specifically targeting glioblastoma cells. It enabled effective delivery of combinational protein and chemotherapeutic drugs by engineered MSC and nanocomposite, respectively. In an in vivo migration model, the hybrid spheroid showed higher nanocomposite retention in the tumor tissue compared with the single MSC approach, leading to enhanced tumor inhibition in a heterotopic glioblastoma murine model. Taken together, this system integrates the merits of cell- and nanoparticle- mediated drug delivery with the tumor-homing characteristics of MSC to advance targeted combinational cancer therapy.

Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications

“…By this method, the content of PTX was~48 pg per cell, much higher than that reported by other techniques (~1-20 pg per cell), while maintaining cell phenotype. In another study, Suryaprakash et al engineered hybrid spheroids of TRAIL-expressing MSCs and drug-loading NPs to actively deliver combinational therapeutics for treatments of glioblastoma [82]. The intra-tumor injection of these platforms significantly improved their retention and increased the amount of delivered NPs at tumor site for enhanced anti-tumor effects [82].…”

“…In another study, Suryaprakash et al engineered hybrid spheroids of TRAIL-expressing MSCs and drug-loading NPs to actively deliver combinational therapeutics for treatments of glioblastoma [82]. The intra-tumor injection of these platforms significantly improved their retention and increased the amount of delivered NPs at tumor site for enhanced anti-tumor effects [82]. Despite rapid progress in therapeutic cell engineering, there has been no clinical trial which utilizes stem cells as carriers for targeting NPs to tumors so far.…”

<p>Overcoming the Blood–Brain Barrier: Successes and Challenges in Developing Nanoparticle-Mediated Drug Delivery Systems for the Treatment of Brain Tumours</p>

“…121 In a recent work, a hybrid system consisting of MSC spheroids and methotrexate (MTX)-loaded nanoparticles was engineered, in order to increase retention at tumour site: this system improved tumour inhibition in a heterotopic glioblastoma murine model. 122 Even though drug-loaded MSC are a promising strategy, some major issues should be considered, such as the fact that the conjugation of nanodrugs to MSC surface could affect the tumour homing ability, as demonstrated by a lot of studies carried out on brain tumour xenografts.…”

Advanced biomedical applications based on emerging 3D cell culturing platforms

“…9). 95 Generating MSC cells in spheroids firstly increase their tumour targeting ability and boost the payload of anticancer drugs.…”