Biology subjects

Palanikumar, L.

Publications and source records attributed to Palanikumar, L..

3 recordsLinked to original sources

bioRxiv2025

pH-Responsive Near Infrared Light Triggered Hydroxyapatite Nanoparticles for Targeted Photothermal Cancer Therapy

Photothermal therapy (PTT), which utilizes photothermal agents (PTAs) to induce localized hyperthermia within tumors upon light irradiation, has emerged as a promising cancer treatment strategy. However, low water solubility, poor in vivo circulation stability and a lack of tumor specificity of many common PTAs limit their applicability. To address these issues, we have developed a simple, yet highly potent, tumor-targeted nanotheranostic system that consists of lipid/PEG-coated hydroxyapatite nanoparticles (LHAPNs) encapsulating the near-infrared (NIR) photothermal dye IR106 (LHAPNIRs). The lipid coat serves to retain the encapsulated dye and prevent serum protein adsorption and macrophage recognition, which would otherwise destabilize the nanoparticles and hinder their tumor targeting efficiency. Additionally, the coat is functionalized with the tumor-acidity-triggered rational membrane (ATRAM) peptide for efficient and specific internalization into tumor cells in the mildly acidic microenvironment of tumors. The nanoparticles facilitated real-time fluorescence and thermal imaging of tumors and demonstrated potent NIR-light triggered anticancer activity in vitro and in vivo, without adversely affecting healthy tissue, leading to markedly prolonged survival. Our results demonstrate that the biocompatible and biodegradable ATRAM-functionalized LHAPNIRs (ALHAPNIRs) effectively combine dual-mode diagnostic imaging with targeted cancer PTT.

bioengineering↗

bioRxiv2023

pH-responsive upconversion mesoporous silica nanospheres for combined multimodal diagnostic imaging and targeted photodynamic and photothermal cancer therapy

Photodynamic therapy (PDT) and photothermal therapy (PTT) have garnered considerable interest as non-invasive cancer treatment modalities. However, these approaches remain limited by low solubility, poor stability and inefficient targeting of many common photosensitizers (PSs) and photothermal agents (PTAs). To overcome these limitations, we have designed biocompatible and biodegradable tumor-targeted upconversion nanospheres with imaging capabilities. The multifunctional nanospheres consist of a sodium yttrium fluoride core doped with lanthanides (ytterbium, erbium and gadolinium) and bismuth selenide (NaYF4:Yb/Er/Gd,Bi2Se3) within a mesoporous silica shell that encapsulates a PS, Chlorin e6 (Ce6), in its pores. NaYF4:Yb/Er converts deeply penetrating near-infrared (NIR) light to visible light, which excites the Ce6 to generate cytotoxic reactive oxygen species (ROS), while the PTA Bi2Se3 efficiently converts absorbed NIR light to heat. Additionally, Gd enables magnetic resonance imaging (MRI) of the nanospheres. The mesoporous silica shell is coated with lipid/polyethylene glycol (DPPC/cholesterol/DSPE-PEG) to ensure retention of the encapsulated Ce6 and minimize interactions with serum proteins and macrophages that impede tumor targeting. Finally, the coat is functionalized with the acidity-triggered rational membrane (ATRAM) peptide, which promotes specific and efficient internalization into cancer cells within the mildly acidic tumor microenvironment. Following uptake by cancer cells in vitro, NIR laser irradiation of the nanospheres caused substantial cytotoxicity due to ROS production and hyperthermia. The nanospheres facilitated tumor MRI and thermal imaging, and exhibited potent NIR laser light-induced antitumor effects in vivo via combined PDT and PTT, with no observable toxicity to healthy tissue, thereby substantially prolonging survival. Our results demonstrate that the ATRAM-functionalized, lipid/PEG-coated upconversion mesoporous silica nanospheres (ALUMSNs) offer multimodal diagnostic imaging and targeted combinatorial cancer therapy.

bioengineering↗

bioRxiv2020

Protein mimetic amyloid inhibitor potently abrogates cancer-associated mutant p53 aggregation and restores tumor suppressor function

Missense mutations in p53 are severely deleterious and occur in over 50% of all human cancers. The vast majority of these mutations are located in the inherently unstable DNA-binding domain (DBD), many of which destabilize the domain further and expose its aggregation-prone hydrophobic core, prompting self-assembly of mutant p53 into inactive cytosolic amyloid-like aggregates. Screening an oligopyridylamide library, previously shown to inhibit amyloid formation associated with Alzheimers disease and type II diabetes, identified a tripyridylamide, ADH-6, that potently abrogates self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD. Moreover, ADH-6 effectively targets and dissociates mutant p53 aggregates in human cancer cells, which restores p53s transcriptional activity, leading to cell cycle arrest and apoptosis. Notably, ADH-6 treatment substantially shrinks xenografts harboring mutant p53 and prolongs survival, while exhibiting no toxicity to healthy tissue. This study demonstrates the first successful application of a bona fide small-molecule amyloid inhibitor as an anticancer agent.

cancer biology↗