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An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
Targeted hollow pollen silica nanoparticles for enhanced intravesical therapy of bladder cancer
Lulu Wang1,2, Fan Qi1,3, Luopeng Bi3
1Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, Jilin, China. zhangh@ciac.ac.cn.
Abstract:
Bladder cancer (BC), such as non-muscle invasive bladder cancer (NMIBC), has a significantly high recurrence rate even after intravesical therapy because traditional intravesical chemotherapeutic drugs have short retention time in the bladder and lack efficient uptake in BC cells. Pollen structure usually shows potent adhesion ability to tissue surfaces, different from traditional electronic interaction or covalent binding. 4-Carboxyphenylboric acid (CPBA) has high affinity to sialic acid residues that are overexpressed on BC cells. In the present study, hollow pollen silica (HPS) nanoparticles (NPs) were prepared and modified with CPBA to form CHPS NPs, which could be further loaded with pirarubicin (THP) to form THP@CHPS NPs. THP@CHPS NPs showed high adhesion to skin tissues and could be more efficiently internalized by a mouse bladder cancer cell line (MB49) than THP, inducing more significant apoptotic cells. After intravesical instillation into a BC mouse model through an indwelling catheter, THP@CHPS NPs could more significantly accumulate at the bladder than THP at 24 h post-instillation, and after 8 days of intravesical treatments, magnetic resonance imaging (MRI) revealed that the bladders treated with THP@CHPS NPs showed more smooth bladder lining and more reduction in size and weights than those with THP. Moreover, THP@CHPS NPs exhibited excellent biocompatibility. THP@CHPS NPs hold great potential for intravesical treatment of bladder cancer.
Insights
Novel pollen-based nanoparticles (THP@CHPS NPs) demonstrate enhanced bladder cancer cell uptake and retention for intravesical therapy. This approach offers improved bladder cancer treatment with reduced recurrence rates.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Oncology
Background:
- Non-muscle invasive bladder cancer (NMIBC) has high recurrence rates due to poor drug retention and cellular uptake with traditional intravesical therapies.
- Pollen structures offer unique tissue adhesion properties, distinct from conventional binding methods.
- Sialic acid residues are overexpressed on bladder cancer cells, presenting a target for drug delivery.
Purpose of the Study:
- To develop and evaluate hollow pollen silica (HPS) nanoparticles modified with 4-carboxyphenylboric acid (CPBA) for enhanced bladder cancer intravesical treatment.
- To investigate the efficacy of pirarubicin (THP)-loaded modified nanoparticles (THP@CHPS NPs) in a bladder cancer mouse model.
Main Methods:
- Preparation of hollow pollen silica (HPS) nanoparticles and modification with 4-carboxyphenylboric acid (CPBA) to create CHPS nanoparticles.
- Loading of pirarubicin (THP) onto CHPS nanoparticles to form THP@CHPS nanoparticles.
- In vitro evaluation of cellular uptake and apoptosis induction in MB49 bladder cancer cells; in vivo assessment of bladder accumulation, therapeutic efficacy, and biocompatibility in a bladder cancer mouse model using magnetic resonance imaging (MRI).
Main Results:
- THP@CHPS nanoparticles exhibited superior adhesion to tissues and enhanced internalization by MB49 cells compared to free THP, leading to increased apoptosis.
- Intravesical instillation in a bladder cancer mouse model showed significantly higher bladder accumulation of THP@CHPS NPs than THP at 24 hours.
- Eight days of treatment resulted in smoother bladder lining, reduced bladder size and weight in the THP@CHPS NP group compared to the THP group, with excellent biocompatibility.
Conclusions:
- THP@CHPS nanoparticles demonstrate potent adhesion and efficient drug delivery for intravesical bladder cancer therapy.
- This novel nanoparticle system significantly improves therapeutic outcomes and reduces tumor burden in a preclinical bladder cancer model.
- THP@CHPS NPs represent a promising platform for overcoming limitations of current intravesical bladder cancer treatments.
