Probing the fluorination effect on the self-assembly characteristics, fate and antitumor efficacy of paclitaxel prodrug nanoassemblies.

Small-molecule prodrug nanoassembly is emerging as an efficient platform for chemotherapy. The self-assembly stability plays a vital role on the drug delivery efficiency of prodrug nanoassembly. It is reported that fluoroalkylation could improve the self-assembly stability of amphiphilic polymers by utilizing the unique fluorination effect.

Self-stabilized Pt(IV) amphiphiles by precise regulation of branch length for enhanced chemotherapy.

A surge of platinum(IV) compounds are utilized or investigated in cancer treatment but their therapeutic outcomes have been greatly compromised by remaining adverse effects and limited antitumor performance, attributable to nonspecific distribution and insufficient activation in tumor site. Herein, we designed a series of disulfide bond introduced Pt(IV)-lipid prodrugs with different branch length, all of which are able to self-stabilize into nanomedicine and be activated by high intracellular glutathione (GSH) level. The impact of precise modification of these prodrugs on their assembly stability, pharmacokinetics and cytotoxicity was probed to establish a connection between chemical structure and antiproliferation efficiency.

Disulfide bond based cascade reduction-responsive Pt(IV) nanoassemblies for improved anti-tumor efficiency and biosafety.

The platinum-based drugs prevail in the therapy of malignant tumors treatment. However, their clinical outcomes have been heavily restricted by severe systemic toxicities. To ensure biosafety and efficiency, herein, we constructed a disulfide bond inserted Pt(IV) self-assembled nanoplatform that is selectively activated by rich glutathione (GSH) in tumor site.

Irinotecan and berberine co-delivery liposomes showed improved efficacy and reduced intestinal toxicity compared with Onivyde for pancreatic cancer.

Onivyde is the first irinotecan (IRI) nanoliposome that could improve pharmacokinetics and tumor biodistribution of irinotecan. Although FDA approves Onivyde for the treatment of pancreatic cancer patients who are not effective for GEM, the gastrointestinal toxicity caused by Onivyde is still a problem to be solved in clinical application. Berberine (BER), an isoquinolone alkaloid extracted from several different plants, has been reported to exhibit beneficial effect in alleviating intestinal mucositis and generating synergistic anticancer effect in combination with cytotoxic drugs.

Remote loading paclitaxel-doxorubicin prodrug into liposomes for cancer combination therapy.

The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX--DOX (PSD).

Improved antitumor activity and tolerability of cabazitaxel derived remote-loading liposomes.

The value of the clinical application of chemotherapeutic drugs is dependent on both systemic toxicity and treatment efficacy. Dose intensification and high tolerability suggest the potential for clinical cancer therapy. In this study, we developed a novel strategy for reconstructing a drug molecule into remote-loading liposomes.

Single-ligand dual-targeting irinotecan liposomes: Control of targeting ligand display by pH-responsive PEG-shedding strategy to enhance tumor-specific therapy and attenuate toxicity.

Along with the malignant proliferation of tumor requiring nutrients, the expression of L-type amino acid transporter 1(LAT1) and amino acid transporter B (ATB) in cancer cells is up-regulated that can be used as new targets for active targeting of tumor. However, since normal cells also express amino acid transporters in small amounts, traditional ligand-exposure drug delivery systems are potentially toxic to the body. Therefore, we designed a smart-response drug delivery system that buries the tyrosine ligand in PEG hydration layer at normal tissues and exposes the ligand by cleaving the pH-sensitive bond of PEG at the tumor site.

Simple weak-acid derivatives of paclitaxel for remote loading into liposomes and improved therapeutic effects.

Liposomes are among the most successful nanocarriers; several products have been marketed, all of which were prepared by active loading methods. However, poorly water-soluble drugs without ionizable groups are usually incorporated into the lipid bi-layer of liposomes by passive loading methods, with serious drug leakage during blood circulation. Furthermore, there have been few improvements in their anti-cancer activity and safety.

Tyrosine modified irinotecan-loaded liposomes capable of simultaneously targeting LAT1 and ATB for efficient tumor therapy.

As the demand for nutrients in malignant proliferation of tumors increases, the L-type amino acid transporter 1(LAT1) and amino acid transporter B (ATB) of tumor cells are more highly expressed than normal cells which can be used as new targets for active targeting of cancer. However, drug delivery systems often require multi-target design to achieve simultaneous targeting of different receptors or transporters due to the heterogeneity of the tumor. Here we utilized triethylamine-sucrose octasulfate gradient to actively encapsulate irinotecan into the introliposomal aqueous phase.

Effective co-encapsulation of doxorubicin and irinotecan for synergistic therapy using liposomes prepared with triethylammonium sucrose octasulfate as drug trapping agent.

The combination regimen of irinotecan (IRI) and doxorubicin (DOX) for cancer treatment has been frequently exploited in clinical studies, but face challenges in design of efficacious combination drug delivery systems. Here we demonstrate a novel nanoliposome constructed by triethylammonium sucrose octasulfate gradient loading method for co-delivering the two therapeutic agents. In vitro cytotoxicity of IRI, DOX and their combinations against breast cancer cells (4T-1), non-small cell lung cancer cells (A549) and colon cancer cells (HT-29) was evaluated to screen optimal synergistic ratio of the two drugs.