Ultrahigh Penetration and Retention of Graphene Quantum Dot Mesoporous Silica Nanohybrids for Image Guided Tumor Regression

Funding: This work was supported by Department of Biotechnology, Government of India. J.C. acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). We thank the staff of animal house, NCCS, Pune for supporting us during animal studies. We also thank Mr. Sumit for the discussion and Dr. Mukesh K. Kumawat for providing GQDs.So far, near-infrared (NIR) light responsive nanostructures have been well-defined in cancer nanomedicine. However, poor penetration and retention in tumors are the limiting factors. Here, we report the ultrahigh penetration and retention of carbanosilica (graphene quantum dots, GQDs embedded mesoporous silica) in solid tumors. After NIR light exposure, quick (0.5 h) emission from the tumor area is observed that is further retained up to a week (tested up to 10 days) with a single dose administration of nanohybrids. Emissive and photothermally active GQDs and porous silica shell (about 31% drug loading) make carbanosilica a promising nanotheranostic agent exhibiting 68.75% tumor shrinking compared to without NIR light exposure (34.48%). Generated heat (∼52 °C) alters the permeability of tumor enhancing the accumulation of nanotheranostics into the tumor environment. Successive tumor imaging ensures the prolonged follow-up of image guided tumor regression due to synergistic therapeutic effect of nanohybrids.publishersversionpublishe

Poly(d,l‑lactide-<i>co</i>-glycolide) Surface-Anchored Biotin-Loaded Irinotecan Nanoparticles for Active Targeting of Colon Cancer

A poly(d,l-lactide-co-glycolide) (PLGA) copolymer was synthesized using the ring-opening polymerization of d,l-lactide and glycolide monomers in the presence of zinc proline complex in bulk through the green route and was well characterized using attenuated total reflectance–Fourier transform infrared, 1H and 13C nuclear magnetic resonance, gel permeation chromatography, differential scanning calorimetry, X-ray diffraction, matrix-assisted laser desorption/ionization time-of-flight, etc. Furthermore, PLGA-conjugated biotin (PLGA-B) was synthesized using the synthesized PLGA and was employed to fabricate nanoparticles for irinotecan (Ir) delivery. These nanoparticles (PLGA-NP-Ir and PLGA-B-NP-Ir) were tested for physicochemical and biological characteristics. PLGA-B-NP-Ir exhibited a stronger cellular uptake and anticancer activity as compared to PLGA-NP-Ir in CT-26 cancer cells (log p < 0.05). The accumulation and retention of fluorescence-labeled nanoparticles were observed to be better in CT-26-inoculated solid tumors in Balb/c mice. The PLGA-B-NP-Ir-treated group inhibited tumor growth significantly more (log p < 0.001) than the untreated control, PLGA-NP-Ir, and Ir-treated groups. Furthermore, no body weight loss, hematological, and blood biochemical tests demonstrated the nanocarriers’ nontoxic nature. This work presents the use of safe PLGA and the demonstration of a proof-of-concept of biotin surface attached PLGA nanoparticle-mediated active targeted Ir administration to combat colon cancer. To treat colon cancer, PLGA-B-NP-Ir performed better due to specific active tumor targeting and greater cellular uptake due to biotin