Faculty Directory

Organo-Inorganic Biomaterials for Theranostics composite biomaterials for simultaneous therapy and imaging of solid tumors.

Plasmonic nanomaterials for Photothermal Therapy to combat undruggable advanced cancers.

Targeted combinatorial nanomedicines that target multiple molecular mechanisms in advanced tumors

Hydrogels are three dimensional cross linked network of hydrophilic polymers, extensively used for biomedical, biotechnological and pharmaceutical applications. The functionality of hydrogel could be enhanced by synthesizing hydrogel nanocomposites that can both enable controlled release of drugs in a cancerous microenvironment and  NIR -induced localized  heat generation for combined chemo-photothermal therapy (Chemo-PTT), a potent anticancer therapeutic approach. Herein, Navneet et al developed a plasmonically active hydrogel with carboxyl methyl chitosan (CMC) as the supporting matrix cross linked with ZIF8 nanoparticles and Mg ²⁺. The ZIF8 nanoparticles were loaded in situ with the ultra small gold nanoparticles (USGNPs) and anticancer drug, curcumin for localized Chemo-PTT. The plasmonic hydrogel (PHG) showed visco-elastic and self-healing properties governed by the supramolecular interaction between ZIF8 and CMC.  The injectable PHG exhibited  photothermal conversion efficiency of ⁓41%. Chemo-PTT with Cur-PHG effectively inhibited 4T1 breast cancer under both  in vitro and in vivo conditions. The biocompatible PHG was found to release UsGNPs from tumor tissue post intra tumoral injection followed by predominant distribution in liver and kidney. Due to the size of UsGNPs (<5nm), they were consistently detected in the urine over the period of treatment confirming overall degradable nature of PHG that delivers a localized outcome with negligible systemic toxicity.

More info:  Navneet Kaur, Mimansa, Priyanka Sharma, Panangattukara Praveen Kumar, Prakash P. Neelakandan, Asifkhan Shanavas,  ACS Applied Polymer Materials, 2022  ( https://doi.org/10.1021/acsapm.2c01646 )

Graphitic carbon nitride (also known as g-CN or g-C₃N ₄ ) has the intrinsic ability to generate electron–hole pairs under visible light illumination, resulting in the generation of reactive oxygen species (ROS). We report g-CN quantum dots (g-CNQDs) as a standalone photodynamic transducer for imparting significant oxidative stress in glioma cells, manifested by the loss of mitochondrial membrane potential. With an optimized treatment time, visible light source, and exposure window, the photodynamic treatment with g-CNQDs could achieve ∼90% cancer cell death via apoptosis. The g-CNQDs, otherwise biocompatible with normal cells up to 5 mg/mL, showed ∼20% necrotic cancer cell death in the absence of light due to membrane damage induced by a charge shielding effect at the acidic pH prevailing in the tumor environment. Acute toxicity analysis in C57BL/6 mice with intravenously injected g-CNQDs at a 20 mg/kg dose showed no signs of inflammatory response or organ damage.

More info:  Pranjali Yadav, Mimansa, Kamalakannan Kailasam*, Asifkhan Shanavas*, ACS Applied Bio Materials, 2022  ( https://doi.org/10.1021/acsabm.1c01219 )

Disintegrable inorganic nanoclusters (GIONs) with gold seed (GS) coating of an iron oxide core with a primary nanoparticle size less than 6 nm were prepared for theranostic applications. The GIONs possessed a broad near-infrared (NIR) absorbance at ∼750 nm because of plasmon coupling between closely positioned GSs on the iron oxide nanoclusters (ION) surface, in addition to the ∼513 nm peak corresponding to the isolated GS. The NIR laser-triggered photothermal response of GIONs was found to be concentration-dependent with a temperature rise of ∼8.5 and ∼4.5 °C from physiological temperature for 0.5 and 0.25 mg/mL, respectively. The nanoclusters were nonhemolytic and showed compatibility with human umbilical vein endothelial cells up to a concentration of 0.7 mg/mL under physiological conditions. The nanoclusters completely disintegrated at a lysosomal pH of 5.2 within 1 month. With an acute increase of over 400% intracellular reactive oxygen species soon after γ-irradiation and assistance from Fenton reaction-mediated supplemental oxidative stress, GION treatment in conjunction with radiation killed ∼50% of PLC/PRF/5 hepatoma cells. Confocal microscopy images of these cells showed significant cytoskeletal and nuclear damage from radiosensitization with GIONs. The cell viability further decreased to ∼10% when they were sequentially exposed to the NIR laser followed by γ-irradiation. The magnetic and optical properties of the nanoclusters enabled GIONs to possess a T₂ relaxivity of ∼223 mM^–1 s^–1and a concentration-dependent strong photoacoustic signal toward magnetic resonance and optical imaging. GIONs did not incur any organ damage or evoke an acute inflammatory response in healthy C57BL/6 mice. Elemental analysis of various organs indicated differential clearance of gold and iron via both renal and hepatobiliary routes.

More info:  Pranjali Yadav, Mimansa, Rafika Munawara, Kanchan Kapoor, Shubhra Chaturvedi, Kamalakannan Kailasam, Samir Kumar Biswas, Dhirendra Bahadur, Rohit Srivastava, Anil Kumar Mishra, Asifkhan Shanavas, ACS Biomaterials Science & Engineering, 2022 (https://doi.org/10.1021/acsbiomaterials.1c01579).

Subnanometer-sized metal nanoclusters (NCs) with diameters less than < 2 nm have emerged as promising materials in biomedical applications. Here we report the synthesis of near- infrared emitting (NIR) Au14 nanoclusters using a small therapeutic molecule D-penicillamine (DPA) as a surface stabilizing agent. We have characterized the morphology and composition of as-synthesized NCs using electron microscopy and mass spetrsometry techniques. The photophysics of the NCs was investigated using UV-Vis and photoluminescence (PL) spectroscopy. We found molecular like absorption features with three distinctive absorption bands at 390 nm, 456 nm, 590 nm, and a photoemission band at 696 nm. We found Au NCs specifically inhibited cancer cells in a dose-dependent manner through preferential uptake and imparting significant intracellular ROS. They did not show any acute toxicity in C57BL/6 mice at a dosage of 10 mg/Kg with predominant accumulation in the kidney at the end of 24 hours.

More info: Dipankar Bain, Mimansa, Aarti Devi, Subarna Maity, Asifkhan Shanavas*, Amitava Patra*, ACS Sustainable Chemistry & Enigneering, 2022 (https://doi.org/10.1021/acssuschemeng.2c03605)

Host derived serum proteome stabilised red-emitting gold quantum clusters (or Au-QC-NanoSera or QCNS) of size range ~2 nm have been synthesised in a first reported study. The host serum was taken from bovine, murine and human origins to establish the proof of concept. In-vitro biocompatibility with normal murine L929 fibroblast cells and radiosensitisation ability against PLC/PRF/5 hepatoma cells was established. A concentration dependant radiosensitisation effect of QCNS at differential γ-radiation doses was observed with almost 90% killing of cancer cells at a radiation dose of 5Gy. Acute and subacute safety, and non-immunogenicity of autologously derived QCNS was established in in-bred C57BL/6 mice. The biodistribution analysis revealed that the QCNS were effectively cleared from the body over a course of 28 days and were found to pose no major threat to the proper functioning and morphology of the mice.

More info: Kritika Sood, Pranjali Yadav, Manu Jamwal, Reena Das, Asifkhan Shanavas,(2023) Nanotheranostics,.7(3):316-326 (https://doi.org/10.7150/ntno.82978)

We report drug nanocrystals stabilized with host specific serum proteins with high loading (~63% w/w). The human serum derived curcumin nanoparticles (Cur-NanoSera) showed  superior in vitro anti-cancer efficiency compared to free drug with substantial hemocompatibility. The pre-adsorbed protein coating impeded further protein corona formation  even with repeated serum exposures. Acute & sub-acute toxicity evaluation post single and dual  injections of C57BL/6 mice derived Cur-NanoSera showed no prominent inflammatory response  or organ damage in the in-bred mice. Passive accumulation of Cur-NanoSera in tumor tissue  significantly suppressed its growth in a syngeneic breast tumor model in addition to controlling  tumor burden associated splenomegaly.

More info: Mimansa, Manu Jamwal, Reena Das, Asifkhan Shanavas, Biomacromolecules, 2022  (https://doi.org/10.1021/acs.biomac.2c00907)

Advanced breast cancer is known to be highly evasive to conventional therapeutic regime with a five-year survival rate of less than 30 % compared to over 90 % for early stages. Although several new approaches are being explored to improve the survival outcome, there is still some room for equipping existing drugs such as lapatinib (LAPA) and doxorubicin (DOX) to fight the systemic disease. LAPA is associated with poorer clinical outcomes in HER2 negative patients, the ability to also target EGFR has warranted its use in recent clinical trials. It is also poorly absorbed post oral administration and possesses low aqueous solubility. DOX on the other hand is avoided in vulnerable patients in advanced stages due to its pronounced off-target toxicity. To overcome the pitfalls of the drugs, we have fabricated a nanomedicine co-loaded with LAPA & DOX and stabilized with glycol chitosan, a biocompatible polyelectrolyte. With a loading content of ~11.5 % and ~15 % respectively, LAPA and DOX in a single nanomedicine showed synergistic action against triple negative breast cancer cells in comparison to physically mixed free drugs. The nanoparticles showed a time dependent association with cancer cells thereon inducing apoptosis leading to ~80 % cell death. The nanomedicine was found to be acutely safe in healthy Balb/c mice and could negate DOX induced cardio toxicity. The combination nanomedicine significantly inhibited both primary 4T1 breast tumor and its spread to lung, liver, heart and kidney compared to pristine drug controls. These preliminary data indicate bright prospects for the nanomedicine to be effective against metastatic breast cancer.

More info: Navneet Kaur, Priyanka Sharma, Mimansa, Mahendran Jaganathan, Rafika Munawara, Anjali Aggarwal, Asifkhan Shanavas, Drug Delivery and Translational Research, 2023 (https://doi.org/10.1007/s13346-023-01335-6)

Green synthesis of gold nanodendrites involving autologous serum proteins as both a template and stabilizer is reported. The nano dendrites, also termed ‘Plasmonic NanoSera’ (PNS), with a size ∼ 150 nm, possess anisotropic dense branches with a broad extinction cross section across the visible-near infrared (I & II) regions. The PNS, with a photothermal conversion efficiency of ∼58%, demonstrated significant phototoxicity in cancer cells associated with elevated intracellular reactive oxygen species. The PNS did not cause acute toxicity with intravenous administration at 20 mg kg−1 dosage. Intra-tumoral injection of autologous mouse serum protein-derived PNS followed by 808 nm Laser irradiation generated a ∼78% higher localized temperature rise compared to a saline control in the 4T1 breast tumor model, thereby suppressing both the tumor growth and tumor burden-associated splenomegaly. This proof-of-concept study validates the preclinical safety and host-specific photothermal efficacy of PNS.

More info: Mimansa, Smriti Bansal, Pranjali Yadav and Asifkhan Shanavas, Materials Advances, 2023 (https://doi.org/10.1039/D3MA00576C)