Polysuccinimide-based nanoparticle: A nanocarrier with drug release delay and zero burst release properties for effective theranostics of cancer

Abstract

We have developed a novel pH-responsive delivery system consisting of oleylamine-modified polysuccinimide (PSI) nanoparticles (NPs) whereby NPs remained stable and started to release bioactive agents after 8.5 h with maximal release acquired after 36 h under physiological pH. Our NPs did not exhibit any burst release of drug, which is a key advantage in anti-cancer targeted drug delivery system. Here, the NPs function as a carrier for bioactive agents such as Curcumin and IR-780 dye whereby the former exerts its intrinsic anti-cancer abilities, the latter confers photothermal treatment application and bimodal imaging ability using photoacoustic and fluorescence imaging. In vitro and in vivo results establish that administration of folate receptors targeting PSI-NPs in U87MG model effected in a substantial decrease in tumour and photothermal laser exposure at 808 nm further ablated tumours to an almost total eradication. Our dual loaded targeted NPs demonstrated selectivity through enhanced accumulation and retention in tumours as indicated by multi-spectral optoacoustic tomography (MSOT) and fluorescence imaging (FI). Loading of Curcumin and IR-780 into PSI-NPs improved its bioavailability, allowing Curcumin to be administered into the circulation system and retention in tumours which led to the simultaneous application for a successful targeted, synergistic photothermal treatment and bimodal imaging using MSOT and FI.