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AS1411 aptamer/RGD dual functionalized theranostic chitosan-PLGA nanoparticles for brain cancer treatment and imaging
Mahima Chauhan1, Sonali2, Saurabh Shekhar1
1Department of Pharmacy, School of Medical and Allied Sciences, GD Goenka University, Gurugram 122103, India.
Abstract:
Conventional chemotherapy and poor targeted delivery in brain cancer resulting to poor treatment and develop resistance to anticancer drugs. Meanwhile, it is quite challenging to diagnose/detection of brain tumor at early stage of cancer which resulting in severity of the disease. Despite extensive research, effective treatment with real-time imaging still remains completely unavailable, yet. In this study, two brain cancer cell specific moieties i.e., AS1411 aptamer and RGD are decorated on the surface of chitosan-PLGA nanoparticles to improve targeted co-delivery of docetaxel (DTX) and upconversion nanoparticles (UCNP) for effective brain tumor therapy and real-time imaging. The nanoparticles were developed by a slightly modified emulsion/solvent evaporation method. This investigation also translates the successful synthesis of TPGS-chitosan, TPGS-RGD and TPGS-AS1411 aptamer conjugates for making PLGA nanoparticle as a potential tool of the targeted co-delivery of DTX and UCNP to the brain cancer cells. The developed nanoparticles have shown an average particle size <200 nm, spherical in shape, high encapsulation of DTX and UCNP in the core of nanoparticles, and sustained release of DTX up to 72 h in phosphate buffer saline (pH 7.4). AS1411 aptamer and RGD functionalized theranostic chitosan-PLGA nanoparticles containing DTX and UCNP (DUCPN-RGD-AS1411) have achieved greater cellular uptake, 89-fold improved cytotoxicity, enhanced cancer cell arrest even at lower drug conc., improved bioavailability with higher mean residence time of DTX in systemic circulation and brain tissues. Moreover, DUCPN-RGD-AS1411 have greatly facilitated cellular internalization and higher accumulation of UCNP in brain tissues. Additionally, DUCPN-RGD-AS1411 demonstrated a significant suppression in tumor growth in brain-tumor bearing xenograft BALB/c nude mice with no impressive sign of toxicities. DUCPN-RGD-AS1411 has great potential to be utilized as an effective and safe theranostic tool for brain cancer and other life-threatening cancer therapies.
Insights
This study developed targeted nanoparticles for brain cancer therapy. These nanoparticles improve drug delivery and enable real-time imaging, showing significant tumor suppression with minimal toxicity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Conventional chemotherapy faces challenges in brain cancer treatment due to poor drug targeting and resistance.
- Early brain tumor detection remains difficult, often leading to disease progression.
- Effective brain tumor treatments combined with real-time imaging are still lacking.
Purpose of the Study:
- To develop targeted nanoparticles for co-delivery of docetaxel and upconversion nanoparticles for brain cancer therapy and imaging.
- To functionalize chitosan-PLGA nanoparticles with AS1411 aptamer and RGD for enhanced brain tumor targeting.
- To evaluate the theranostic potential of these nanoparticles in vitro and in vivo.
Main Methods:
- Chitosan-PLGA nanoparticles were synthesized using an emulsion/solvent evaporation method.
- Nanoparticles were decorated with AS1411 aptamer and RGD moieties for targeted delivery.
- Co-delivery of docetaxel (DTX) and upconversion nanoparticles (UCNP) was achieved within the nanoparticles.
- In vitro and in vivo studies were conducted to assess cellular uptake, cytotoxicity, drug release, bioavailability, and tumor suppression.
Main Results:
- Developed nanoparticles (<200 nm) showed spherical shape, high drug/UCNP encapsulation, and sustained DTX release.
- AS1411 aptamer and RGD functionalized nanoparticles (DUCPN-RGD-AS1411) demonstrated enhanced cellular uptake and 89-fold improved cytotoxicity.
- Significant tumor growth suppression was observed in brain-tumor bearing mice with no apparent toxicity.
- Improved bioavailability and higher UCNP accumulation in brain tissues were noted.
Conclusions:
- Targeted co-delivery of DTX and UCNP using AS1411/RGD functionalized nanoparticles is a promising strategy for brain cancer theranostics.
- The developed DUCPN-RGD-AS1411 nanoparticles offer enhanced efficacy and safety for brain tumor treatment and imaging.
- This theranostic approach holds potential for treating brain cancer and other life-threatening malignancies.
