Gold nanoparticle-directed autophagy intervention for antitumor immunotherapy via inhibiting tumor-associated macrophage M2 polarization

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.

Adverse drug reactions induced by traditional Chinese medicine treatment for new coronavirus pneumonia during the medical observation period / 药学实践杂志

Objective To investigate the characteristics of the adverse drug reaction (ADR) in the traditional Chinese medicine (TCM) treatment followed the "COVID-19 Diagnosis and Treatment Program (trial version 7)" during the medical observation period, and to provide a guideline for rational clinical drug use. Methods 9 TCM induced ADR were collected from CNKI, Wanfang database and PubMed. Statistical analysis was conducted on gender, age, occurrence time, involved system/organ, treatment, outcome and relevance evaluation. Results 61 literatures were collected according to the inclusion and exclusion criteria with 70 cases and 5 TCM prescriptions. There was no significant bias in gender. The age span was large. Most ADR occurred within 1 day after administration. The involved systems/organs are extensive, mainly on the skin and its accessories. The most common therapeutic drugs were antihistamines and steroids, and other medications are mainly for symptom treatment. The turnaround time was 1 h in most cases (47%). Conclusions During the observation period, the incident population was widely distributed and there was no obvious characteristics. Medication monitoring should be reinforced to reduce the ADR incidence.

Preparation and characterization of co-delivery of doxorubicin and elacridar in nanoparticles / 药学实践杂志

Objective To establish methods for the determination of doxorubicin and elacridar, and prepare PLGA nanoparticles for the co-delivery of doxorubicin and elacridar.Methods Ultraviolet spectrophotometry (UV) and high performance liquid chromatography (HPLC) were used to establish the determination method of doxorubicin and elacridar, respectively;co-delivery nanoparticles system was prepared by nanoprecipitation method, and optimizing the prescription was by adjusting the dosage ratio of the two drugs to investigate the particle size,morphology, encapsulation efficiency (EE), drug loading (DL) and in vitro release.Results The linearity of doxorubicin was better in the rang of 1 to 40 μg/ml, A=0.021C+0.002,r=0.999 5;the linearity of elacridar was better in the rang of 0.5 to 100 μg/ml,A=120 742.462 6C+1 974.570 4,r=1.000 0;the particle size was about 50 nm;transmission electron microscope (TEM) showed that nanoparticles were round in shape and had a good dispersion;EE of doxorubicin and elacridar were 56.58%、51.66%,respectively, DL of doxorubicin and elacridar were 1.48%、1.85%,respectively,the molar ratio of two drugs was about 1∶1;the nanoparticles released slowly in vitro.Conclusion The established methods of doxorubicin and elacridar were convenient and efficient, accurate and repeatable.The Co-delivery nanoparticles system was well dispersionand smaller size, which could be used for further studies.

The preparation and the cell uptake of polymer vesicles modified with dual ligands / 药学实践杂志

Objective To construct an active targeting drug delivery system‐polymer vesicles(PVs), and examined the cellular uptake. Methods Maleimide‐ polyethylene glycol‐poly(lactic‐co‐glycolic acid)(MAL‐PEG‐PLGA)was used as carrier materials to prepare PVs by self‐assembling. And then PVs was modified by Tf and Tet‐1(Tf/Tet‐1‐PVs). To evaluate its ac‐tive targeting, coumarin‐6 was used as a fluorescent probe to analyze cellular uptake of PVs for both BCEC and Neuro‐2a cells. Results PVs was about 80 nm with rounded shape and had obvious film structure. Tf/Tet‐1‐PVs exhibited a significant role in promoting cellular uptake for both BCEC and Neuro‐2a cells compared with control and single ligand‐modified group. Conclusion PVs modified with dual ligands could promote the cell uptake for both brain capillary cells and nerve cells.