Deep tumor-penetrating nano-delivery strategy to improve diagnosis and therapy in patient-derived xenograft(PDX)oral cancer model and patient tissue

Nanoprodrugs that are directly assembled by prodrugs attract considerable attention with high anticancer potentials.However,their stability and efficiency of tumor-targeted delivery remain a major challenge in practical biomedical applications.Here,we report a new deep tumor-penetrating nano-delivery strategy to achieve enhanced anti-cancer performance by systematic optimization of a porphyrin-doxorubicin-based nanoprodrug using various PEGylations/crosslinks and co-administration of targeting peptide iRGD.Polyethylene glycols(PEGs)with different molecular weights and grafts are employed to crosslink the nanoprodrug and optimize size,charge,tumor accumulation and penetration,and anti-cancer efficiency,etc.The tumor penetration was validated in syngeneic oral cancer mouse models,patient-derived xenograft(PDX)models,and oral cancer tissue from patients.The optimized nanoprodrug co-administrated with iRGD remarkably enhances the accumulation and penetration both in tumor vascular and PDX tumor tissue.It is effective and safe to improve in vivo therapeutic efficacy via the passive tumor targeting dependent and independent mode.Our tumor-penetrating nano-delivery strategy is promising to strengthen the nanoprodrugs in clinical implementation.

A mitochondria-targeting lipid——small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model

Hybrid lipid-nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles.Here we developed a kind of lipid-small molecule hybrid nanoparticles(LPHNPs) for imaging and treatment in an ortho topic glioma model.LPHNPs were prepared by engineering the co-assembly of lipids and an amphiphilic pheophorbide a-quinolinium conjugate(PQC),a mitochondria-targeting small molecule.Compared with the pure nanofiber self-assembled by PQC,LPHNPs not only preserve the comparable antiproliferative potency,but also possess a spherical nanostructure that allows the PQC molecules to be administrated through intravenous injection.Also,this co-assembly remarkably improved the drug-loading capacity and formulation stability against the physical encapsulation using conventional liposomes.By integrating the advantages from liposome and PQC molecule,LPHNPs have minimal system toxicity,enhanced potency of photodynamic therapy(PDT) and visualization capacities of drug biodistribution and tumor imaging.The hybrid nanoparticle demonstrates excellent curative effects to significantly prolong the survival of mice with the orthotopic glioma.The unique co-assembly of lipid and small molecule provides new potential for constructing new liposome-derived nanoformulations and improving cancer treatment.