Stem cell membrane vesicle–coated nanoparticles for efficient tumor‐targeted therapy of orthotopic breast cancer

Abstract

Nanoparticles‐based drug delivery strategies have been widely researched for cancer therapy. However, most of them are expected to accumulate in tumor sites via the enhanced permeability and retention (EPR) effect, which is insufficient to deliver the loaded drug into tumors. Cell membrane–camouflaged nanoparticles have obtained much attention for their excellent stability and long blood circulation and reduced the macrophage cells uptake in drug delivery. Herein, bone marrow–derived mesenchymal stem cell membrane vesicle (SCV)–coated paclitaxel (PTX)–loaded poly (lactide‐co‐glycolide) (PLGA) nanoparticles (SCV/PLGA/PTX) were fabricated as the efficient orthotopic breast cancer–targeted drug delivery system. The SCV/PLGA/PTX showed excellent stability, more controlled PTX release, and more effective antitumor effect in vitro. After administration in vivo, SCV/PLGA/PTX exhibited the long‐term retention and enhanced accumulation at tumor sites due to the immune escape and mesenchymal stem cell–mimicking cancer‐targeting capacity. As expected, the SCV/PLGA/PTX could significantly suppress the primary tumor growth by increased apoptosis and necrosis areas within tumor tissues and attenuated the toxic side effects of PTX in 4T1 orthotopic breast cancer model. The study indicated the mesenchymal stem cell membrane coating strategy was highly efficient for targeted drug delivery, which provided a new insight for precise and effective breast cancer treatment.

Cell-mediated and cell membrane-coated nanoparticles for drug delivery and cancer therapy

“…Celland cell membrane-based drug carriers exhibiting intrinsic properties of in vivo biology have been shown to overcome the challenges faced by synthetic NP-based drug carriers and achieve acceptable toxicity and better biocompatibility than their synthetic counterparts [7][8][9][10][11][12] . Major advantages of using cell-and cell membrane-based drug carriers include provision of immune escape and specific tumor targeting imparted by the cell membrane proteins leading to improved EPR in cancer therapies, and an ability to generate desired cytotoxic immunomodulatory effects via cell surface engineering, leading to tumor regression [13][14][15][16][17][18] .…”

Biomimetic Nanocarriers for Cancer Target Therapy

“…The group of Tian [56] showed how PLGA NPs loaded with paclitaxel (PTX) and coated with mesenchymal stem cell membranes can be effective in tumor chemotherapy in a orthotopic breast cancer in mouse, increasing time of circulation of NPs and the uptake, and displaying a controlled release of the payload in an efficient manner while avoiding important side effects ( Figure 5). In another recent study [57], PLGA NPs loaded with DOX were covered with umbilical cord MSC cells and tested on MHCC97-H liver tumor, exhibiting an inhibition tumor growth rate of about 78% in vivo.…”

“…The group of Tian [ 56 ] showed how PLGA NPs loaded with paclitaxel (PTX) and coated with mesenchymal stem cell membranes can be effective in tumor chemotherapy in a orthotopic breast cancer in mouse, increasing time of circulation of NPs and the uptake, and displaying a controlled release of the payload in an efficient manner while avoiding important side effects ( Figure 5 ).…”

“…Schematization of PLGA NPs loaded with paclitaxel (PTX) covered with stem cell membranes and their mechanism of tumor target delivery in orthotopic breast cancer in mouse. Reproduced with permission from Ref [56]…”

Cancer Cell Membrane Technology for Cancer Therapy

“…[22] Further, repeated injections of PEGylated systems promote splenic synthesis, leading to an accelerated blood clearance. [23] To overcome the above limitations, the recent trend in cancer therapy is the surface mimicking of the nanocarriers by coating them with ghost cell membrane, [24] such as red blood cells (RBCs), [25] Leukocytes, [26] platelets, [27] neutrophils, [28] macrophages, [29] dendritic cells, [30] cancer cells, [31] stem cells, [32] exosomes [33] etc. Each of them provides a fascinating set of advantages.…”