All-stage targeted therapy for the brain metastasis from triple-negative breast cancer

Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood-brain barrier (BBB) and blood-tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.

A pentapeptide enabled AL3810 liposome-based glioma-targeted therapy with immune opsonic effect attenuated

AL3810, a molecular dual inhibitor of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), has earned the permission of phase II clinical trial for tumor treatment by China FDA. As a reversible ATP-competitive inhibitor, AL3810 targets ATP-binding site on intracellular region of VEGFR and FGFR, whereas, AL3810 lacking interplay with extracellular region of receptors rendered deficient blood-brain tumor barrier (BBTB) recognition, poor brain penetration and unsatisfactory anti-glioma efficacy. Integrin

Efficacy of inverso isomer of CendR peptide on tumor tissue penetration

The dense extracellular matrix and high interstitial fluid pressure of tumor tissues prevent the ability of anti-tumor agents to penetrate deep into the tumor parenchyma for treatment effects. C-end rule (CendR) peptides can enhance the permeability of tumor blood vessels and tumor tissues binding to neuropilin-1 (NRP-1), thus aiding in drug delivery. In this study, we selected one of the CendR peptides (sequence RGERPPR) as the parent l-peptide and substituted d-amino acids for the l-amino acids to synthesize its inverso peptide (RGERPPR). We investigated the NRP-1 binding activity and tumor-penetrating ability of (RGERPPR). We found that the binding affinity of (RGERPPR) with NRP-1 and the cellular uptake was significantly higher than that of RGERPPR. Evans Blue tests revealed that (RGERPPR) exhibited improved tumor-penetrating ability in C6, U87 and A549 tumor-bearing nude mice. Using nude mice bearing A549 xenograft tumors as a model, we found that the rate of tumor growth in the group co-administered with (RGERPPR) and gemcitabine (Gem) was significantly lower than the gemcitabine-treated group with a tumor suppression rate (TSR%) of 55.4%. Together, our results demonstrate that (RGERPPR) is a potential tumor-penetrating peptide.

From Moral Experience to Care giving: the Theoretical and Practical Paths of Medical Humanities / 中国医学伦理学

Most of the current medical humanities education focuses on the moral aspects without good theoreti-cal basis and specific practices on the medical institution and daily life.The article dates back to the origins of So-cial Science based on the concept caregiving put forward by the medical anthropologist Arthur Kleinman,and states that the ultimate purpose of Social Science is to make response to the social suffering and provide caregiving for it.Caregiving as moral experience is response to social suffering and attracts much importance,because it pro-vides both the theoretical basis and practical means for the current medical humanities education.Its characteristics of caregiving as moral experience to social suffering and caregiving as reciprocity meet the demands of current notion of Big health in China.

Preliminary investigations into surface molecularly imprinted nanoparticles for Helicobacter pylori eradication

This paper reports investigations into the preparation and characterization of surface molecularly imprinted nanoparticles (SMINs) designed to adhere to Helicobacter pylori (H. pylori). Imprinted nanoparticles were prepared by the inverse microemulsion polymerization method. A fraction of Lpp20, an outer membrane protein of H. pylori known as NQA, was chosen as template and modified with myristic acid to facilitate its localization on the surface of the nanoparticles. The interaction between these SMINs with the template NQA were evaluated using surface plasmon resonance (SPR), change in zeta potential and fluorescence polarization (FP). The results were highly consistent in demonstrating a preferential recognition of the template NQA for SMINs compared with the control nanoparticles. In vitro experiments also indicate that such SMINs are able to adhere to H. pylori and may be useful for H. pylori eradication.