Self-indicating, fully active pharmaceutical ingredients nanoparticles (FAPIN) for multimodal imaging guided trimodality cancer therapy

Abstract

Conventional drug delivery systems contain substantial amounts of excipients such as polymers and lipids, typically with low drug loading capacity and lack of intrinsic traceability and multifunctionality. Here, we report fully active pharmaceutical ingredient nanoparticles (FAPIN) which were self-assembled by minimal materials, but seamlessly orchestrated versatile theranostic functionalities including: i) self-delivery: no additional carriers were required, all components in the formulation are active pharmaceutical ingredients; ii) self-indicating: no additional imaging tags were needed. The nanoparticle itself was composed of 100% imaging agents, so that the stability, drug release, subcellular dispositions, biodistribution and therapeutic efficacy of FAPINs can be readily visualized by ample imaging capacities, including energy transfer relay dominated, dual-color fluorogenic property, near-infrared fluorescence imaging and magnetic resonance imaging; and iii) highly effective trimodality cancer therapy, encompassing photodynamic-, photothermal- and chemo-therapies. FAPINs were fabricated with very simple material (a photosensitizer-drug conjugate), unusually achieved ∼10 times better in vitro antitumor activity than their free counterparts, and were remarkably efficacious in patient-derived xenograft (PDX) glioblastoma multiforme animal models. Only two doses of FAPINs enabled complete ablation of highly-malignant PDX tumors in 50% of the mice.

A polymer-free, biomimicry drug self-delivery system fabricatedviaa synergistic combination of bottom-up and top-down approaches

“…We recently developed a new type of self-indicating and self-delivery fully active pharmaceutical ingredients nanoparticles (FAPIN) based on the drug-photosensitizer conjugates (named PI) consisting of Pheophorbide A (Pa) and Irinotecan (Ir) through an ester bond 37 . We demonstrated that PI mediated light treatment not only produced heat and reactive oxygen species(ROS) but also triggered the release of chemotherapeutic drug at the tumor sites, resulting in synergistic anticancer effects in vivo.…”

Conducting Polymeric Nanocomposites with a Three-Dimensional Co-flow Microfluidics Platform

“…Smaller nanocomposites represent a greater surface-area-to-volume ratio; thus, they are to release the drug much more rapidly, which may result in high local API concentrations that could potentially lead to unwanted side effects. Accordingly, a broad size distribution means poor control over the API delivery and release, making it harder to determine a suitable therapeutic dose for the patient [11]. Such failure of control is driving the demand for production methods that reduce polydispersity.…”

Trojan Horse nanotheranostics with dual transformability and multifunctionality for highly effective cancer treatment

“…In comparison with other reported non-PEGylated full API nanoparticles thus far 21 , 40 – 42 , pPhD NPs yielded 100% CCR and showed better anti-tumour efficacy, due to their excellent multimodal therapeutic functions, PEGylated cross-linkage and dual-transformability. By comparing with the multimodal full API nanoparticles that we developed, such as upPhD NPs in this work and PaIr NPs 43 , the anti-tumour efficacy of pPhD NPs was also superior, which can be ascribed to their excellent dual-transformability and PEGylated cross-linkage. pPhD NPs could be conveniently prepared by simply using biocompatible PEG as the only excipient, the DOX and Pa as the APIs.…”