Nanocomplex combinatorials and PRC1 novel targets combat metastatic liver cancer

14 Feb 2022
Nanocomplex combinatorials and PRC1 novel targets combat metastatic liver cancer

Liver cancer remains one of the major causes of cancer death around the world, and most patients are diagnosed in advanced stages of cancer with poor sensitivity to chemotherapeutic agents and drug resistance.

For solid tumours lack of selectivity to cancer cells leading to damage to normal tissues and adverse side effects are a major concern.

Therefore, innovative treatment approaches in HCC are urgently needed.

Optimised targeted nanoparticles can deliver drugs at a sustained rate directly to cancer cells for a prolonged period may provide better efficacy and lower toxicity for treating solid tumours is promising.

Biocompatible polymeric biomaterials have drawn a tremendous attraction as chemotherapeutic delivery modality. Anticancer nanomedicines based on drug delivery therapy are an important means of increasing treatment efficiency and avoiding undesirable side effects.            

Researchers at Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India developed polymeric PLGA block- nanocomplexes encapsulating antimitotic agents; Combretastatin A4 or 2-Methoxyestradiol, along with functionalization of a targeting moiety; Cetuximab.  

The combinatorial approach of targeted CA4 and 2 ME nanocomplexes treatment triggered the therapeutic effects against metastatic liver cancer in SCID mice ectopic and orthotopic models says Dr. Radhika Poojari, Scientist and lead author of the study at IIT Bombay, Mumbai, India.

It exhibited significant tumour growth inhibition, and prevented lung metastasis. We found potent microtubule depolymerisation, antiproliferative, apoptosis induction, and potent vascular shutdown activities against metastatic HCC on treatment with combinatorial targeted nanocomplexes.

PRC1 is a Protein regulator of cytokinesis 1. PRC1 has been reported to contribute to cancer proliferation, metastasis, and tumorigenesis.

Combinatorial targeted nanocomplexes treatment significantly reduced the PRC1 expression against metastatic HCC, a novel target for the therapeutic response. This was embarked for the first time, a breakthrough finding.

Toxicity studies revealed combinatorial nanocomplexes with good tolerance and a safe delivery modality.

Histopathological and ultrastructural studies depicted combinatorial targeted nanocomplexes treatment ameliorated the pathological impairments against metastatic liver cancer.

The study was conducted in collaboration with scientists and researchers team at Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Navi Mumbai, Board of Radiation and Isotope Technology (BRIT), Navi Mumbai, and Omega laboratories, Pune, India culminating into a fruitful outcome.

This study establishes the foundation for the near future early-stage clinical trial of the combinatorial targeted nanocomplexes for the treatment of liver cancer malignancies.

1. Radhika Poojari, Bhabani Mohanty, Vijay Kadwad, Dayaram Suryawanshi, Pradip Chaudhari, Bharat Khade, Rohit Srivastava, Sanjay Gupta, Dulal Panda. Combinatorial Cetuximab targeted polymeric nanocomplexes reduce PRC1 level and abrogate growth of metastatic hepatocellular carcinoma in vivo with efficient radionuclide uptake. Nanomedicine: Nanotechnology, Biology, and Medicine (2022)