Scope and Objectives

Smart materials are recent advancements in cancer theranostics i.e Diagnosis and Therapeutics. We in India, have developed an indigenous biodegradable nanosystem (4 patents filed) that could be used for low dose X-ray irradiation or photothermal therapy with suitable external light trigger non-invasive. The same nanosystem could be deployed for diagnosis or tracking of cancer region as well. These smart nanosystems are capable of homing into tumor region by Enhanced permeation and retention (EPR effect), eliminating the need for tagging with costly antibodies. Our biodegradable nanosystem is capable of identifying solid tumors in the early stages and with the aid of external trigger, we could simultaneously treat the tumor. This novel technology will eradicate the need for tertiary hospital establishments and could be used as non invasive means to diagnose or treat cancer patients even in remote areas and low resource region. Objectives 1.Synthesis and Characterization of biodegradable nanosystems. 2.In vivo optimization of the CT contrast enhancement (imaging) and laser or Xray dose or gold nanoparticle size variations for effective hyper thermic or radiation therapy effect for tumor cell ablation in mouse models. 3. Start of Phase I Clinical Trial to understand the toxicity and efficacy profile of the biodegradable nanosystem in humans.

Deliverables

Our goal is to transfer this novel technology from lab to clinic. We intend to develop measure and optimize the effect of Photothermal therapy/ low dose X-ray based radiotherapy in tumor tissues while keeping the surrounding organs safe. Combining with real-time imaging, this will also enable us to validate the efficacy of this novel treatment approach. The beneficiaries include cancer patients (oral, breast, prostate, cervical cancer, retinoblastoma etc.). When commercialized, this will be the first indigenously developed biodegradable nanoparticle for photothermal treatment of cancer in the world. The current photo-thermally active nanoparticles being developed (by other groups in the world - in clinical trials) are non-biodegradable. Our product is biodegradable and has faster renal clearance without compromising the efficacy in killing cancer cells. This project also involves development of low cost NIR lasers which shall further reduce the cost of Photothermal Therapy making it affordable to all.

Videos

https://youtu.be/uC8-zDiURKQ

Scientific Output

We have developed a biodegradable nanosystem (Lipos-Au NPs), evaluated its efficacy in-vitro and in-vivo. Incorporation of anti-cancer drugs and their triggered release at the tumor site to improve the therapeutic efficacy and to achieve synergistic results is also explored in-vitro and in-vivo. Development a new photothermal material (lipid-polymeric hybrid particles) and investigating the degradability efficacy of these particles is in progress. The genotoxicty of Lipos-Au NPs at different concentrations is completed. Laser irradiation time for the therapy has also been optimized.

Results and outcome till date

The biodegradable nanosystem has been synthesized and the photothermal efficacy of Lipos-Au (model drug loaded) both in-vitro and in-vivo was evaluated. A small pilot study involving the treatment groups have shown that adjuvant therapy along with photothermal therapy is much beneficial. We have also attempted to understand the dynamics of the hydrophobic drugs with trigger time and the overall therapeutic efficiency was evaluated. We have optimized the laser irradiation time from the histopathological observations in mice with Lipos-Au NPs, at twice the therapeutic concentration and two laser irradiation times. The genotoxicity of Lipos-Au NPs was evaluated using two tester strains of the Salmonella typhimurium i.e. TA 100 & TA 98 at different concentrations by the Ames salmonella test.

Societal benefit and impact anticipated

This technology will benefit all cancer patients suffering from solid tumors like (oral, breast, prostate etc.). As India has a large number of oral cancer patients (due to tobacco use), affordable treatment becomes essential to minimize the burden on healthcare. This technology can be adopted with minimal resource settings, thereby providing affordable cancer care in urban as well as remote rural locations. There are not many diode laser manufactures in India. This project will result in the development of low cost NIR lasers, which can be manufactured in India itself with the help of Industry partner. The project's goal of "identifying and treating cancer using smart nanosystem" is highly beneficial for the Indian society.

Next steps

Publications and reports

1. Surya Prakash Singh, Syed Baseeruddin Alvi, Deepak Bharadwaj, Anula Divyash Singh, Sasidhar Venkata Manda, Rohit Srivastava, Aravind Kumar Rengan, NIR triggered liposome gold nanoparticles entrapping curcumin as in situ adjuvant for photothermal treatment of skin cancer, International Journal of Biological Macromolecules. https://doi.org/10.1016/j.ijbiomac.2017.11.163. 2. Pranjali Yadav, Surya Prakash Singh, Aravind Kumar Rengan, Asifkhan Shanavas, Rohit Srivastava, Gold Laced Bio-macromolecules for Theranostic Application, International Journal of Biological Macromolecules. https://doi.org/10.1016/j.ijbiomac.2017.10.124. 3. Deepak S. Chauhan , Amirali B. Bukhari, Gayathri Ravichandran, Ramkrishna Gupta, Liya George, Radhika Poojari, Aravind Ingle, Aravind K. Rengan , Asifkhan Shanavas, Rohit Srivastava & Abhijit De, Enhanced EPR directed and Imaging guided Photothermal Therapy using Vitamin E Modified Toco-Photoxil, Scientific Reports (2018) 8:16673, DOI:10.1038/s41598-018-34898-3 4. Syed B. Alvi, Tejaswini Appidi, Deepak Pemmaraju, Minhas G., Surya P. singh, Afreen Begum, Veeresh Bantal, Rohit Srivastava, Nooruddin Khan, Aravind Kumar Rengan, Timing the Therapeutic Trigger: Analyzing the Dynamics of Hydrophobic Drug Delivery by Early Photothermal Trigger. Submitted to International Journal for review.

Patents

1. An Indian patent DETECTION KIT FOR DIAGNOSIS OF CERVICAL CANCER BY QUANTIFICATION OF VISUAL INSPECTION OF ACETIC ACID has been filed with IPA No. 016604 CHE 2018. 2. An Indian patent FLUORESCENT POLYETHYLENE GLYCOL has been filed with IPA No. 030149 CHE 2018. 3. An Indian patent LIPOSOMAL NANO FORMULATION FOR TREATMENT OF CANCER has been filed with IPA No. 35668/CHE/2018.

Scholars and Project Staff

Research scholar: Appidi Tejaswini Junior Research Scholar Aug 2017-till date. Manpower: Lavleen Bhati Junior Research fellow Feb 2018- Sep 2018.

Challenges faced

None.

Other information

None.