the accurate prediction of protein stability is one of the most challenging goals in protein formulation and delivery. in this study, a gradient rp-hplc method is described for the separation of human growth hormone (hgh) variants as deamidated and oxidized forms. the methodology employed a polymeric poly (styrene-co-divinylbenzene) column and a 1ml/min flow rate of a linear gradient of 0.1% v/...

New treatments are needed for brain metastasis, which is associated with high morbidity and mortality. Two novel cellular and gene therapy modalities were evaluated in xenograft models for human breast cancer. The individual and especially the combined treatments with alloreactive cytotoxic T lymphocytes and replicating retroviral vectors coding for prodrug activating enzymes followed later wit...

The tumor microenvironment is notably enriched with a broad spectrum of proteases. The proteolytic specificities of peptide substrates provide modular chemical tools for the rational design of cell-impermeable prodrugs that are specifically activated by proteases extracellularly in the tumor microenvironment. Targeting cell-impermeable prodrug activation to tumor microenvironment will significa...

A reliable approach is developed to formulate a targeted lipid-coated nanomedicine based on UCNP and co-loaded with CO-prodrug vitamin E, which can convert NIR light UV photon release CO for synergistical cancer therapy E.

Many drugs suffer from an extensive first-pass metabolism leading to drug inactivation and/or production of toxic metabolites, which makes them attractive targets for prodrug design. The classical prodrug approach, which involves enzyme-sensitive covalent linkage between the parent drug and a carrier moiety, is a well established strategy to overcome bioavailability/toxicity issues. However, th...

Short amphiphilic oligo(ethylene glycol)–oligolactide fragments were used to chemically modify a hydrophobic and toxic taxane drug, which induced the self-assembly of resultant prodrug entities in aqueous media for intravenous administration.

We have designed a targeted systemic suicide gene therapy that combines the advantages of tumor-selective gene expression, using the human telomerase promoter (hTERT), with the beneficial effects of an oncolytic adenovirus to deliver the gene for the prodrug-activating enzyme carboxypeptidase G2 (CPG2) to tumors. Following delivery of the vector (AdV.hTERT-CPG2) and expression of CPG2 in cancer...

The differences in micro-environment between cancer cells and the normal ones offer the possibility to develop stimuli-responsive drug-delivery systems for overcoming the drawbacks in the clinical use of anticancer drugs, such as paclitaxel, doxorubicin, and etc. Hence, we developed a novel endosomal pH-sensitive paclitaxel (PTX) prodrug micelles based on functionalized poly(ethylene glycol)-po...

A simultaneously photo-cleavable and activatable prodrug-backboned block copolymer (BCP) micelle strategy is demonstrated. Without light treatment, the micelles stay silent and inactivated, being biocompatible to normal tissues. Concurrent chain cleavage of BCP micelles and the activation of Pt(IV) prodrug could be temporally and spatially triggered by UV or even visible light for precise antic...

The first attempt of constructing pH responsive supramolecular prodrug micelles based on cucurbit[8]uril is reported. The obtained prodrug micelles are found to be able to inhibit proliferation of cancer cells. It is anticipated that this facile strategy may open a novel avenue for the development of multifunctional drug delivery systems.