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Bromelain surface modification increases the diffusion of silica nanoparticles in the tumor extracellular matrix
Alessandro Parodi1, Seth G Haddix, Nima Taghipour
1Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.
Abstract:
Tumor extracellular matrix (ECM) represents a major obstacle to the diffusion of therapeutics and drug delivery systems in cancer parenchyma. This biological barrier limits the efficacy of promising therapeutic approaches including the delivery of siRNA or agents intended for thermoablation. After extravasation due to the enhanced penetration and retention effect of tumor vasculature, typical nanotherapeutics are unable to reach the nonvascularized and anoxic regions deep within cancer parenchyma. Here, we developed a simple method to provide mesoporous silica nanoparticles (MSN) with a proteolytic surface. To this extent, we chose to conjugate MSN to Bromelain (Br-MSN), a crude enzymatic complex, purified from pineapple stems, that belongs to the peptidase papain family. This surface modification increased particle uptake in endothelial, macrophage, and cancer cell lines with minimal impact on cellular viability. Most importantly Br-MSN showed an increased ability to digest and diffuse in tumor ECM in vitro and in vivo.
Insights
Researchers developed Bromelain-conjugated mesoporous silica nanoparticles (Br-MSN) to overcome the tumor extracellular matrix barrier. This novel drug delivery system enhances therapeutic diffusion into deep tumor regions, improving cancer treatment efficacy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Biology
Background:
- The tumor extracellular matrix (ECM) hinders drug delivery and limits therapeutic efficacy in cancer.
- Conventional nanotherapeutics struggle to penetrate deep into nonvascularized, anoxic tumor regions.
- Overcoming the ECM barrier is crucial for effective cancer treatment.
Purpose of the Study:
- To develop a novel nanoparticle system capable of degrading the tumor ECM.
- To enhance the diffusion and penetration of therapeutic agents into solid tumors.
- To improve the efficacy of cancer nanomedicine.
Main Methods:
- Conjugation of mesoporous silica nanoparticles (MSN) with Bromelain, a proteolytic enzyme.
- Characterization of Bromelain-conjugated MSN (Br-MSN) for surface modification.
- In vitro and in vivo evaluation of Br-MSN's ability to digest and diffuse within tumor ECM.
- Assessment of Br-MSN cellular uptake and impact on cell viability.
Main Results:
- Surface modification with Bromelain enhanced nanoparticle uptake in various cell lines.
- Br-MSN demonstrated an increased capacity to digest and penetrate tumor ECM.
- The Br-MSN system showed improved diffusion in both in vitro and in vivo tumor models.
- Cellular viability was minimally affected by the Br-MSN surface modification.
Conclusions:
- Bromelain-conjugated mesoporous silica nanoparticles effectively degrade the tumor ECM.
- Br-MSN offers a promising strategy to overcome drug delivery barriers in solid tumors.
- This approach has the potential to significantly improve the therapeutic outcomes in cancer treatment.
