A biomimetic antitumor nanovaccine based on biocompatible calcium pyrophosphate and tumor cell membrane antigens.

Currently, the cancer immunotherapy has made great progress while antitumor vaccine attracts substantial attention. Still, the selection of adjuvants as well as antigens are always the most crucial issues for better vaccination. In this study, we proposed a biomimetic antitumor nanovaccine based on biocompatible nanocarriers and tumor cell membrane antigens. Briefly, endogenous calcium pyrophosphate nanogranules with possible immune potentiating effect are designed and engineered, both as delivery vehicles and adjuvants. Then, these nanocarriers are coated with lipids and B16-OVA tumor cell membranes, so the biomembrane proteins can serve as tumor-specific antigens. It was found that calcium pyrophosphate nanogranules themselves were compatible and possessed adjuvant effect, while membrane proteins including tumor associated antigen were transferred onto the nanocarriers. It was demonstrated that such a biomimetic nanovaccine could be well endocytosed by dendritic cells, promote their maturation and antigen-presentation, facilitate lymph retention, and trigger obvious immune response. It was confirmed that the biomimetic vaccine could induce strong T-cell response, exhibit excellent tumor therapy and prophylactic effects, and simultaneously possess nice biocompatibility. In general, the present investigation might provide insights for the further design and application of antitumor vaccines.

A Lipid Micellar System Loaded with Dexamethasone Palmitate Alleviates Rheumatoid Arthritis.

Glucocorticoids have been confirmed to be effective in the treatment of a variety of inflammatory diseases. However, their application encounters limitations in terms of tissue distribution and bioavailability in vivo. To address these key issues, we designed and developed a nanopreparation by using egg yolk lecithin/sodium glycocholate (EYL/SGC) and utilize such mixed micelles (MMs) to encapsulate dexamethasone palmitate (DMP) for the treatment of rheumatoid arthritis (RA). The prepared DMP-MMs had an average particle size of 49.18 ± 0.43 nm and were compared with an emulsion-based dexamethasone palmitate. Pharmacokinetic and in vivo fluorescence imaging showed that mixed micelles had higher bioavailability and targeting efficiency in inflammatory sites. An arthritis rat model was established via induction by Complete Freund's Adjuvant (CFA), followed by the efficacy studies by the observations of paw volume, histology, spleen index, pro-inflammatory cytokines, and CT images. It was confirmed that intravenous injection of DMP-MMs exhibited advantages in alleviating joint inflammation compared with the emulsion system. Composed of pharmaceutical adjuvants only, the nanoscale mixed micelles seem a promising carrier system for the RA treatment with lipophilic drugs.

Peptide-Drug Conjugate-Based Nanocombination Actualizes Breast Cancer Treatment by Maytansinoid and Photothermia with the Assistance of Fluorescent and Photoacoustic Images.

To develop a highly efficient strategy against tumors, here, a nanocombination (PDC/P@HCuS) was designed and constructed to actualize chemo-phototherapy with the assistance of fluorescence (FL) and photoacoustic (PA) images. First, a type of organic-inorganic hybrid nanosystem (P@HCuS) was engineered by coupling the fluorescence-labeled amphiphilic fPEDC copolymer on the surface of hollow mesoporous copper sulfide nanoparticle (HCuS), in which HCuS was used as a photothermal and PA agent; fPEDC as a stabilizer, chromophore, and redox/pH-sensitive gatekeeper; and both of them as drug carriers. Then, a peptide-drug conjugate (cRGD-SMCC-DM1, PDC), as a molecular targeted maytansinoid, was loaded inside of P@HCuS to form PDC/P@HCuS. Next, the PDC/P@HCuS was investigated carefully with or without near-infrared (NIR) laser irradiation. In vitro, the nanocombination exhibited stimuli-responsive drug release, obvious cellular uptake, strong cytotoxicity to tumor cells, significant impact on cell cycle, and cytoskeleton and cellular proteomics as well as evident permeability into the tumor sphere, most of which could be boosted by NIR laser irradiation. In vivo, the nanocombinaiton exerted good FL/PA imaging features and photothermal efficiency, achieved the best antitumor efficacy in the presence of NIR laser irradiation, and showed excellent biosafety. Together, it demonstrated that the PDC/P@HCuS, representing a chemo-phototherapy based on a nanocombination associated with peptide-drug conjugate, could achieve the highly efficient antitumor effect.

A cremophor-free self-microemulsified delivery system for intravenous injection of teniposide: evaluation in vitro and in vivo.

In order to tackle the problems on low water solubility of teniposide, involvement of toxic surfactant in its injection, and the poor stability during infusion, a Cremophor-free teniposide self-microemulsified drug delivery system (TEN-SMEDDS) was prepared for the first time, characterized, and evaluated in comparison with teniposide injection (VUMON) in vitro and in vivo. The optimized formulation contained N, N-dimethylacetamide, medium-chain triglyceride, lecithin, and dehydrated alcohol besides teniposide. The TEN-SMEDDS could form fine droplets with mean diameter of 282 ± 21 nm and zeta potential of -7.5 ± 1.7 mV after dilution with 5% glucose, which were stable within 4 h. The release of teniposide from TEN-SMEDDS and VUMON was similar. However, the pharmacokinetic behavior of TEN-SMEDDS in rats was different from that of VUMON, evidenced by the lower area under the concentration-time curve and larger volume of distribution in emulsion group. Finally, TEN-SMEDDS was found to distribute more teniposide in most tissues, especially in reticuloendothelial system, after intravenous administration to rats. Importantly, brain drug level in TEN-SMEDDS group was higher than or similar to that in control group, although the emulsion system had a lower plasma drug concentration. In conclusion, the novel SMEDDS prepared here, without toxic surfactant and as an oil solution before use, may be potential for clinical use due to its low toxicity and high store stability. It may be favorable for the treatment of some tumors like cerebroma, since it may achieve the relatively higher drug level in brain but lower blood concentration.