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Polydopamine-Based Targeted Nanosystem for Chemo/Photothermal Therapy of Retinoblastoma in a Mouse Orthotopic Model
Bo Jin1, Kexin Lu2, Wenna Gao1
1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Hennan, 450052, People's Republic of China.
Background:
At present, the few photothermal/chemotherapy studies about retinoblastoma that have been reported are mainly restricted to ectopic models involving subcutaneous implantation. However, eyeball is unique physiological structure, the blood-retina barrier (BRB) hinders the absorption of drug molecules through the systemic route. Moreover, the abundant blood circulation in the fundus accelerates drug metabolism. To uphold the required drug concentration, patients must undergo frequent chemotherapy sessions.
Purpose:
To address these challenges above, we need to develop a secure and effective drug delivery system (FA-PEG-PDA-DOX) for the fundus.
Methods:
We offered superior therapeutic efficacy with minimal or no side effects and successfully established orthotopic mouse models. We evaluated cellular uptake performance and targeting efficiency of FA-PEG-PDA-DOX nanosystem and assessed its synergistic antitumor effects in vitro and vivo. Biodistribution assessments were performed to determine the retention time and targeting efficiency of the NPs in vivo. Additionally, safety assessments were conducted.
Results:
Cell endocytosis rates of the FA-PEG-PDA-DOX+Laser group became 5.23 times that of the DOX group and 2.28 times that of FA-PEG-PDA-DOX group without irradiation. The fluorescence signal of FA-PEG-PDA-DOX persisted for more than 120 hours at the tumor site. The number of tumor cells (17.2%) in the proliferative cycle decreased by 61.6% in the photothermal-chemotherapy group, in contrast to that of the saline control group (78.8%). FA-PEG-PDA-DOX nanoparticles(NPs) exhibited favorable biosafety and high biocompatibility.
Conclusion:
The dual functional targeted nanosystem, with the effects of DOX and mild-temperature elevation by irradiation, resulted in precise chemo/photothermal therapy in nude mice model.
Insights
A novel drug delivery system (FA-PEG-PDA-DOX) enhances photothermal chemotherapy for retinoblastoma by improving drug uptake and retention in the eye. This targeted nanosystem offers superior therapeutic efficacy with minimal side effects in preclinical models.
Area of Science:
- Ophthalmology
- Nanotechnology
- Biomedical Engineering
Background:
- Retinoblastoma treatment faces challenges due to the blood-retina barrier (BRB) and rapid drug metabolism in the eye.
- Existing photothermal/chemotherapy studies primarily use ectopic models, not addressing the unique ocular environment.
- Frequent chemotherapy is often required to maintain therapeutic drug concentrations in the fundus.
Purpose of the Study:
- To develop a secure and effective fundus-targeted drug delivery system (FA-PEG-PDA-DOX) for retinoblastoma.
- To overcome the limitations of systemic drug delivery in the unique physiological structure of the eye.
- To create a nanosystem for combined photothermal and chemotherapy with enhanced ocular drug retention.
Main Methods:
- Established orthotopic mouse models for retinoblastoma.
- Synthesized and characterized the FA-PEG-PDA-DOX nanosystem for drug delivery.
- Evaluated cellular uptake, targeting efficiency, and synergistic antitumor effects in vitro and in vivo.
- Conducted biodistribution and safety assessments to determine in vivo retention and biocompatibility.
Main Results:
- FA-PEG-PDA-DOX demonstrated a 5.23-fold increase in cell endocytosis with laser irradiation compared to DOX alone.
- The nanosystem showed sustained fluorescence signal (over 120 hours) at the tumor site, indicating prolonged retention.
- The photothermal-chemotherapy group significantly reduced tumor cell proliferation (61.6% decrease) compared to controls.
- FA-PEG-PDA-DOX nanoparticles exhibited favorable biosafety and high biocompatibility in preclinical assessments.
Conclusions:
- The dual-functional targeted nanosystem (FA-PEG-PDA-DOX) precisely delivered chemotherapy and utilized mild hyperthermia via irradiation.
- This approach achieved effective chemo/photothermal therapy in an orthotopic nude mice model of retinoblastoma.
- The developed nanosystem offers a promising strategy for treating retinoblastoma with improved therapeutic outcomes and safety.
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