Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy

Abstract

Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake. Incorporation of ICG in PGA nanoparticles provided the NIR-absorbing agent with time-dependent altered optical properties in the presence of cathepsin B. Having minimal dark toxicity, the formulation exhibited significant cytotoxicity upon NIR exposure. Combined use of the formulation with saporin, a ribosome-inactivating protein, resulted in synergistically enhanced cytotoxicity attributed to the photo-induced release of saporin from endo/lysosomes. The results suggest that this therapeutic approach can offer significant therapeutic benefit in the treatment of superficial malignancies, such as head and neck tumours.

Plant Ribosome-Inactivating Proteins: Progesses, Challenges and Biotechnological Applications (and a Few Digressions)

“…Nanoparticle-based formulations can promote drug release with a selective activation within the target organ/tissue as a result of different stimuli, such as pH, enzymes, heat, light, etc. Liposomes, polymers and inorganic nanoparticles have been successfully employed for the delivery of protein toxins [ 113 , 114 , 115 ]. A library of cationic lipid-like materials (termed “lipidoids”) was designed and employed to form nanocomplexes with proteins for intracellular delivery.…”

“…Upon cleavage, ICG and saporin became bioavailable within the tumor context, facilitating their cellular uptake. Following irradiation, light causes endo/lysosome disruption with consequent drug release in the cytosol, where saporin exerts its toxic effect [ 114 ]. Another similar approach is the so-called photochemical internalization (PCI) to facilitate protein release to the cytosol after endocytosis of PCI-relevant photosensitizers.…”

Stimuli-responsive drug delivery systems for head and neck cancer therapy

“…Therefore, several studies on the multifunctional lightresponsive DDSs loaded with ICG were reported. Tarassoli et al (2017) developed copolymer nanoparticles loaded with ICG for NIR-trigged head and neck cancer therapy with improved drug accumulation and antitumor effect. Wang, Xie, et al (2019) fabricated ICG-cisplatin nanoparticles for the treatment of OSCC, the coordination bond of which could be cleaved by a NIR-induced photothermal effect of ICG.…”

“…Such dual stimuli-responsive DDSs were widely applied in the phototherapy for HNC. PDT or PTT agents were loaded in pH or MMP sensitive drug carriers for TME controlled drug release and light triggered antitumor treatment (Tarassoli et al, 2017). Meanwhile, chemotherapy agents were also reported co-delivered for the improved chemophoto therapy (Wang, Hu, et al, 2019).…”

Nanotechnology – A promising prospect for cancer diagnostics and therapeutics

“…It has also offered the ability to develop non-invasive and effective theragnostic systems allowing for both 4 diagnosis and treatment with a single agent such as photosensitive cyanine dyes. Another form of nanotechnology-based cancer treatment being developed is localised magnetic hyperthermia using magnetic NPs and more recently thermo-chemotherapy, where traditional chemotherapy agents are combined with magnetic NPs in the same formulation.…”