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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
DNA Base Pairing-Inspired Supramolecular Nanodrug Camouflaged by Cancer-Cell Membrane for Osteosarcoma Treatment
Yucheng Fu1, Guoyu He1, Zhuochao Liu1
1Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China.
Abstract:
Osteosarcoma (OS) is one of the most common bone malignant tumors which mainly develops in adolescents. Although neoadjuvant chemotherapy has improved the prognosis of patients, numerous chemotherapeutic challenges still limit their use. Here, inspired by the Watson-Crick base pairing in nucleic acids, hydrophobic (methotrexate) and hydrophilic (floxuridine) chemo-drugs are mixed and self-assembled into M:F nanoparticles (M:F NPs) through molecular recognition. Then, the obtained NPs are co-extruded with membranes derived from OS cells to form cancer-cell membrane-coated NPs (CCNPs). With protected membranes at the outer layer, CCNPs are highly stable in both physiological and weak acid tumor conditions and possess homologous tumor targeted capability. Furthermore, the proteomic analysis first identifies over 400 proteins reserved in CCNPs, most of them participating in tumor cell targeting and adhesion processes. In vitro studies reveal that CCNPs significantly inhibit the PI3K/AKT/mTOR pathway, which promotes cell apoptosis and cell cycle arrest. More importantly, cell membrane camouflage significantly prolongs the circulation half-life of CCNPs, elevates the drug accumulation at tumor sites, and promotes anti-tumor efficacy in vivo. As a convenient and effective strategy to construct a biomimetic NP with high drug loading ratio, the CCNPs provide new potentials for precise and synergistic antitumor treatment.
Insights
This study introduces cancer-cell membrane-coated nanoparticles (CCNPs) for osteosarcoma (OS) treatment. CCNPs enhance drug delivery and efficacy, offering a promising strategy for precise antitumor therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Osteosarcoma (OS) is a common bone cancer in adolescents, with chemotherapy facing significant challenges.
- Current treatments have limitations, necessitating novel approaches for improved patient outcomes.
Purpose of the Study:
- To develop a novel drug delivery system for osteosarcoma using self-assembled nanoparticles coated with cancer cell membranes.
- To evaluate the efficacy of these cancer-cell membrane-coated nanoparticles (CCNPs) in vitro and in vivo.
Main Methods:
- Hydrophobic (methotrexate) and hydrophilic (floxuridine) drugs were self-assembled into M:F nanoparticles.
- These nanoparticles were coated with osteosarcoma cell membranes to create CCNPs.
- Proteomic analysis identified proteins involved in tumor targeting and adhesion.
- In vitro studies assessed the inhibition of the PI3K/AKT/mTOR pathway, apoptosis, and cell cycle arrest.
- In vivo studies evaluated circulation half-life, tumor accumulation, and anti-tumor efficacy.
Main Results:
- CCNPs demonstrated high stability in physiological and acidic tumor conditions with homologous tumor targeting.
- Proteomic analysis revealed over 400 proteins in CCNPs, many involved in tumor cell targeting and adhesion.
- In vitro, CCNPs significantly inhibited the PI3K/AKT/mTOR pathway, inducing apoptosis and cell cycle arrest.
- In vivo, CCNPs showed prolonged circulation, enhanced tumor drug accumulation, and improved anti-tumor efficacy.
Conclusions:
- CCNPs represent a convenient and effective biomimetic nanoparticle strategy with a high drug loading ratio.
- This approach offers new potential for precise and synergistic antitumor treatment of osteosarcoma.
- The cell membrane camouflage significantly enhances therapeutic outcomes by improving pharmacokinetics and tumor targeting.
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