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Ultrasmall porphyrin-silica core-shell dots for enhanced fluorescence imaging-guided cancer photodynamic therapy
Sadaf Hameed1, Pravin Bhattarai2, Zhuoran Gong3
1Faculty of Science and Technology, University of Central Punjab Lahore 54000 Pakistan.
Abstract:
Clinically used small-molecular photosensitizers (PSs) for photodynamic therapy (PDT) share similar disadvantages, such as the lack of selectivity towards cancer cells, short blood circulation time, life-threatening phototoxicity, and low physiological solubility. To overcome such limitations, the present study capitalizes on the synthesis of ultra-small hydrophilic porphyrin-based silica nanoparticles (core-shell porphyrin-silica dots; PSDs) to enhance the treatment outcomes of cancer via PDT. These ultra-small PSDs, with a hydrodynamic diameter less than 7 nm, have an excellent aqueous solubility in water (porphyrin; TPPS3-NH2) and enhanced tumor accumulation therefore exhibiting enhanced fluorescence imaging-guided PDT in breast cancer cells. Besides ultra-small size, such PSDs also displayed an excellent biocompatibility and negligible dark cytotoxicity in vitro. Moreover, PSDs were also found to be stable in other physiological solutions as a function of time. The fluorescence imaging of porphyrin revealed a prolonged residence time of PSDs in tumor regions, reduced accumulation in vital organs, and rapid renal clearance upon intravenous injection. The in vivo study further revealed reduced tumor growth in 4T1 tumor-bearing bulb mice after laser irradiation explaining the excellent photodynamic therapeutic efficacy of ultra-small PSDs. Thus, ultrasmall hydrophilic PSDs combined with excellent imaging-guided therapeutic abilities and renal clearance behavior represent a promising platform for cancer imaging and therapy.
Insights
Ultra-small, hydrophilic porphyrin-silica dots (PSDs) offer improved cancer treatment via photodynamic therapy (PDT). These nanoparticles enhance tumor targeting and imaging while ensuring rapid clearance, overcoming limitations of current photosensitizers.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Materials Science
Background:
- Clinically used photosensitizers (PSs) for photodynamic therapy (PDT) exhibit poor selectivity, short circulation times, and low solubility.
- These limitations hinder effective cancer treatment and increase toxicity risks.
- Developing novel nanomaterials is crucial to overcome these challenges in PDT.
Purpose of the Study:
- To synthesize ultra-small, hydrophilic porphyrin-based silica nanoparticles (PSDs) for enhanced cancer imaging and PDT.
- To evaluate the physicochemical properties, biocompatibility, and therapeutic efficacy of these novel PSDs.
- To investigate the potential of PSDs as a theranostic platform for breast cancer treatment.
Main Methods:
- Synthesis of core-shell porphyrin-silica dots (PSDs) with hydrodynamic diameters < 7 nm.
- Assessment of aqueous solubility, stability in physiological solutions, and biocompatibility (in vitro).
- Evaluation of tumor accumulation, biodistribution, renal clearance, and in vivo therapeutic efficacy in 4T1 tumor-bearing mice using fluorescence imaging and laser irradiation.
Main Results:
- PSDs demonstrated excellent aqueous solubility, stability, and biocompatibility with negligible dark cytotoxicity.
- Fluorescence imaging showed enhanced tumor accumulation, prolonged residence time, reduced vital organ uptake, and rapid renal clearance of PSDs.
- In vivo studies confirmed reduced tumor growth in mice treated with PSDs and laser irradiation, indicating high photodynamic therapeutic efficacy.
Conclusions:
- Ultra-small hydrophilic PSDs represent a promising platform for advanced cancer imaging and therapy.
- The enhanced tumor targeting, imaging capabilities, and favorable pharmacokinetic profile of PSDs overcome limitations of conventional photosensitizers.
- PSDs offer a potential theranostic approach for improved breast cancer treatment outcomes.
