Meng Li,Aoxiang Luo,Wei Xu,Haoze Wang,Yuanyuan Qiu,Zeyu Xiao,Kai Cui
A visual Raman nano-delivery system (NS) is a widely used technique for the visualization and diagnosis of tumors and various biological processes. Thiophene-based organic polymers exhibit excellent biocompatibility, making them promising candidates for development as a visual Raman NS. However, materials based on thiophene face limitations due to their absorption spectra not matching with NIR (near-infrared) excitation light, which makes it difficult to achieve enhanced Raman properties and also introduces potential fluorescence interference. In this study, we introduce a donor–acceptor (D-A)-structured thiophene-based polymer, PBDB-T. Due to the D-A molecular modulation, PBDB-T exhibits a narrow bandgap of Eg= 2.63 eV and a red-shifted absorption spectrum, with the absorption edge extending into the NIR region. Upon optimal excitation with 785 nm light, it achieves ultra-strong pre-resonant Raman enhancement while avoiding fluorescence interference. As an intrinsically sensitive visual Raman NS for in vivo imaging, the PBDB-T NS enables the diagnosis of microtumor regions with dimensions of 0.5 mm × 0.9 mm, and also successfully diagnoses deeper tumor tissues, with an in vivo circulation half-life of 14.5 h. This research unveils the potential application of PBDB-T as a NIR excited visual Raman NS for microtumor diagnosis, introducing a new platform for the advancement of “Visualized Drug Delivery Systems”. Moreover, the aforementioned platform enables the development of a more diverse range of targeted visual drug delivery methods, which can be tailored to specific regions.
Residual microtumours after surgical resection leading to tumour relapse is one of the major challenges for cancer therapy. Herein, we developed a nano-hybrid oligopeptide hydrogel for topical delivery of a chemotherapeutic drug, docetaxel (DTX), to inhibit the post-surgical tumour recurrence. This nano-hybrid hydrogel (DTX-CTs/Gel) was prepared by encapsulating DTX in cell-penetrating peptide-modified transfersomes followed by embedment in an oligopeptide hydrogel. The obtained DTX-CTs/Gel showed paintable and injectable properties, and could support prolonged retention at the administrated sites after topical administration. DTX-CTs released from the hydrogel presented high skin and tumour penetration capabilities, and increased the accumulation of DTX in the cancer cells leading to enhanced cell death. We showed that the topical delivery of DTX using DTX-CTs/Gel efficiently slowed down the tumour relapse in post-surgical mouse melanoma and breast tumour models.
Integrating these features of acid-activated positively charged surface and size contraction into single nanoparticle would be an effective strategy for enhancing cellular uptake, intratumoral penetration and accumulation. Here, hierarchical responsive micelle (HVDMs) was developed via RAFT reaction as multifunctional polymer-drug conjugate for maximizing penetration and therapeutic effect against MCF-7 tumor by combining positively charged surface with size contraction: surface zeta-potential reversal (−2 to +12 mV) by protonation of PHEME and size contraction (~81–~41 nm) by simultaneous hydrophobic/hydrophilic conversion (pH ≈ 6.7); the disintegration of hydrazone bond between hydrophobic PVB and DOX triggered drug release (pH ≈ 5.0). The in vitro structural stabilization, cellular uptake and anti-proliferative efficiency were significantly higher than other control groups (CVDMs and HSDMs) at pH 6.7. The markedly increased penetration depth, cellular internalization and anti-tumor efficiency were confirmed in 3D MCSs spheroids at pH 6.7, and the ex vivo DOX fluorescence images further verified obvious penetration and accumulation in internal region of solid tumor. The antitumor effect in vivo demonstrated that HVDMs accelerated tumor atrophy, induced intratumoral cells apoptosis and alleviated system toxicity.
危险品化学品经营许可证（带存储）