Drug Release from Gelsolin-Targeted Phase-Transition Nanoparticles Triggered by Low-Intensity Focused Ultrasound
Haocheng Qin1, Rong Teng1, Yan Liu1
1Department of Ultrasound, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, People's Republic of China.
Purpose:
Current strategies for tumour-induced sentinel lymph node detection and metastasis therapy have limitations. It is essential to identify and provide warnings earlier for tumour metastasis to carry out effective clinical interventions. In addition, traditional cancer chemotherapy encounters drastic limitations due to the nonspecific delivery of antitumour drugs and severe side effects. We aimed to exploit the potential of gelsolin (GSN) monoclonal antibody as a targeting agent and perfluorohexane (PFH) as a phase-transition agent to maximize the cytotoxic effect of poly(lactic-co-glycolic acid) (PLGA) nanoparticle-based drug controllable release systems for Hca-F cells.
Methods:
We co-encapsulated PFH and doxorubicin (DOX) into PLGA nanoparticles (NPs) and further conjugated GSN monoclonal antibody onto the surface of NPs to form GSN-targeted phase transition polymer NPs (GSN-PLGA-PFH-DOX) for both imaging and therapy of tumours and metastatic lymph nodes. To promote and trigger drug release on demand, low-intensity focused ultrasound (LIFU) was applied to achieve a controllable release of the encapsulated drug.
Results:
GSN-PLGA-PFH-DOX NPs exhibited characteristics such as a narrow size distribution and smooth surface. GSN-PLGA-PFH-DOX NPs could also specifically bind to Hca-F cells and increase the ultrasound contrast agent (UCA) image contrast intensity. GSN-PLGA-PFH-DOX NPs enable GSN-mediated targeting and biotherapeutic effects as well as LIFU-responsive drug release, resulting in synergistic cytotoxic effects in GSN-overexpressing cells in vitro.
Conclusion:
Our work might provide a strategy for the imaging and chemotherapy of primary tumours and their metastases.
Insights
This study developed targeted nanoparticles for cancer imaging and therapy. These nanoparticles enhance drug delivery and therapeutic effects, offering a new strategy for treating primary tumors and metastases.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Current cancer therapies face limitations in targeting tumors and drug delivery.
- Early detection and treatment of tumor metastasis are crucial for effective clinical intervention.
- Nonspecific drug delivery in chemotherapy leads to severe side effects.
Purpose of the Study:
- To develop a novel nanoparticle system for targeted cancer imaging and therapy.
- To utilize gelsolin (GSN) monoclonal antibody as a targeting agent.
- To employ perfluorohexane (PFH) as a phase-transition agent for controlled drug release.
Main Methods:
- Co-encapsulation of PFH and doxorubicin (DOX) into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs).
- Conjugation of GSN monoclonal antibody onto NP surface to create GSN-targeted phase transition polymer NPs (GSN-PLGA-PFH-DOX).
- Application of low-intensity focused ultrasound (LIFU) to trigger on-demand drug release.
Main Results:
- GSN-PLGA-PFH-DOX NPs demonstrated narrow size distribution and smooth surface.
- NPs specifically bound to Hca-F cells and enhanced ultrasound contrast.
- LIFU-induced drug release resulted in synergistic cytotoxic effects in GSN-overexpressing cells.
Conclusions:
- The developed GSN-PLGA-PFH-DOX NPs offer a promising strategy for imaging and chemotherapy.
- This approach targets both primary tumors and their metastases.
- The study highlights the potential of targeted, ultrasound-responsive nanoparticles in cancer treatment.
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