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Cancer-Cell-Membrane-Coated Nanoparticles with a Yolk-Shell Structure Augment Cancer Chemotherapy
Di Nie1,2, Zhuo Dai1,3, Jialin Li1,3
1Shanghai Institute of Materia Medica , Chinese Academy of Sciences , Shanghai 201203 , China.
Abstract:
Despite rapid advancements in antitumor drug delivery, insufficient intracellular transport and subcellular drug accumulation are still issues to be addressed. Cancer cell membrane (CCM)-camouflaged nanoparticles (NPs) have shown promising potential in tumor therapy due to their immune escape and homotypic binding capacities. However, their efficacy is still limited due to inefficient tumor penetration and compromised intracellular transportation. Herein, a yolk-shell NP with a mesoporous silica nanoparticle (MSN)-supported PEGylated liposome yolk and CCM coating, CCM@LM, was developed for chemotherapy and exhibited a homologous tumor-targeting effect. The yolk-shell structure endowed CCM@LM with moderate rigidity, which might contribute to the frequent transformation into an ellipsoidal shape during infiltration, leading to facilitated penetration throughout multicellular spheroids in vitro (up to a 23.3-fold increase compared to the penetration of membrane vesicles). CCM@LM also exhibited a cellular invasion profile mimicking an enveloped virus invasion profile. CCM@LM was directly internalized by membrane fusion, and the PEGylated yolk (LM) was subsequently released into the cytosol, indicating the execution of an internalization pathway similar to that of an enveloped virus. The incoming PEGylated LM further underwent efficient trafficking throughout the cytoskeletal filament network, leading to enhanced perinuclear aggregation. Ultimately, CCM@LM, which co-encapsulated low-dose doxorubicin and the poly(ADP-ribose) polymerase inhibitor, mefuparib hydrochloride, exhibited a significantly stronger antitumor effect than the first-line chemotherapeutic drug Doxil. Our findings highlight that NPs that can undergo facilitated tumor penetration and robust intracellular trafficking have a promising future in cancer chemotherapy.
Insights
Researchers developed novel cancer cell membrane-camouflaged nanoparticles (CCM@LM) that enhance tumor penetration and intracellular drug delivery for improved chemotherapy efficacy. This biomimetic approach offers a promising strategy for overcoming limitations in current antitumor drug delivery systems.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Current antitumor drug delivery faces challenges with intracellular transport and subcellular drug accumulation.
- Cancer cell membrane (CCM)-camouflaged nanoparticles (NPs) show potential but struggle with tumor penetration and intracellular delivery.
- Inefficient delivery limits the therapeutic efficacy of existing nanomedicines.
Purpose of the Study:
- To develop a novel yolk-shell nanoparticle (CCM@LM) for enhanced chemotherapy.
- To improve tumor penetration and intracellular drug trafficking for improved antitumor effects.
- To investigate the unique internalization and trafficking mechanisms of the designed NPs.
Main Methods:
- Fabrication of a yolk-shell nanoparticle with a mesoporous silica nanoparticle (MSN)-supported PEGylated liposome yolk and CCM coating.
- Evaluation of nanoparticle penetration through multicellular spheroids in vitro.
- Assessment of cellular internalization pathways and intracellular trafficking using microscopy and biochemical assays.
- Co-encapsulation of doxorubicin and mefuparib hydrochloride for combination chemotherapy.
Main Results:
- The yolk-shell structure of CCM@LM facilitated tumor penetration, showing a 23.3-fold increase compared to membrane vesicles.
- CCM@LM exhibited enveloped virus-like cellular internalization via membrane fusion, releasing PEGylated liposomes into the cytosol.
- Efficient cytoskeletal trafficking led to enhanced perinuclear aggregation of the released payload.
- CCM@LM demonstrated significantly stronger antitumor effects than Doxil when co-delivering doxorubicin and mefuparib hydrochloride.
Conclusions:
- CCM@LM nanoparticles possess enhanced tumor penetration and intracellular trafficking capabilities.
- The biomimetic design and unique internalization pathway contribute to improved drug delivery and therapeutic outcomes.
- This nanoplatform holds significant promise for advancing cancer chemotherapy.
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