Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in tumors, which generally exhibit anti-inflammatory M2 phenotypes, and are the key inducers of tumor development, metastasis and drug resistance, and thus becoming a popular target in the field of antitumor immunotherapy.The study and application of nanocarriers optimize TAMs-targeted antitumor therapy.According to the characteristics and functions of TAMs, modulation strategies based on TAMs are elaborated, including TAMs depletion, inhibition of TAMs recruitment and TAMs repolarization.At the same time, in order to apply the above strategies more efficiently and overcome the general off-target problems in treatment, specific TAMs-targeted therapies based on nanocarriers are reviewed and analyzed, including passive targeting to TAMs, active targeting to macrophages and specifically active targeting to M2-TAMs. Finally, based on the limitations of targeting TAMs alone, new therapeutic strategies of targeting both TAMs and tumor cells via nanocarrier based delivery systems are introduced to provide new ideas for the application of these strategies in the field of tumor immunotherapy and combination therapy with other antitumor strategies.

As a typical BCS Ⅱ drug, felodipine exhibits low solubility and high permeability. We herein investigated the effects of different solubilization strategies on the oral absorption of felodipine. Firstly felodipine tablets based on 200 μm, 150 μm and 25 μm particle size of bulk drug were prepared. Meanwhile, felodipine solid dispersion and felodipine nanosuspension with average particle size of (168.90 ± 6.22) nm, PDI of 0.11 ± 0.06 were prepared. The absorption rate, apparent permeability coefficient (Papp), absorption quality in duodenum, jejunum, ileum and colon of rats and in vivo pharmacokinetics of the above different felodipine preparations were investigated. The results of rat single-pass intestinal perfusion showed that the absorption of felodipine preparations in duodenum, jejunum and ileum was better than in colon. Felodipine had a wide absorption window in the small intestine, with the best absorption site in the small intestine. Papp of different felodipine preparations was greater than 2.0 × 10-5 cm/s. Thus, the low solubility was the main factor limiting the absorption. In vivo pharmacokinetic experiments demonstrated the solubilization strategies significantly improved the bioavailability. The bioavailabilities of felodipine tablets with particle sizes of 150 and 25 μm, as well as nanosuspension, and solid dispersion were 138.75%, 173.01%, 208.65% and 314.53% that of the tablets with particle size of 200 μm, respectively. Solubilization strategies can significantly improve the gastrointestinal absorption rate and absorption quality of felodipine, and thus improve its bioavailability, which provides some reference for the research on the improvement of oral absorption of BCS II drugs.

In this study, a polyethylene glycol and dodecaldehyde modified bovine serum albumin (PEG-DSA) was developed, and its feasibility as a new high-efficiency micellar carrier for dasatinib (DAS) was explored.Circular dichroism, 1H NMR, elemental analysis, FT-IR and other methods were used to characterize the material structure and the single factor method was used to optimize the process of PEG-DSA/DAS micelles and non-PEGylated control micelles DSA/DAS.The results indicated that the optimal formulation was obtained with a mass ratio of 4∶1 between PEG-DSA and DAS, with average particle size of (37.21 ± 0.21) nm, polydispersion index (PDI) of (0.24 ± 0.04), Zeta potential of ? (15.68 ± 0.19) mV, drug loading (DL) capacity of (10.22 ± 0.34) %, and encapsulation efficiency (EE) of (42.73 ± 1.15) %. Compared with the currently reported nano-formulations of DAS, the drug loading of PEG-DSA/DAS micellar formulations was significantly increased with potential for further development.

Tumor-associated fibroblasts(TAFs),the most important stromal cells of the tumor microenvironment (TME),have been found to support tumorigenesis and tumor metastasis in a variety of ways,including paracrine, direct contact with cells,immune regulation and extracellular matrix remolding.Therefore,TAFs in the TME have been an optimal target for cancer therapy.In this review,the TAFs targeted therapies are summarized to provide the new strategy for tumor treatments based on the analysis of the location and specific biological phenotypes of TAFs in tumors.

Hypoxia,a salient feature of solid tumors,is often associated with invasiveness,metastasis and resistance to anticancer drugs.The strategies including the use of oxygen-carriers based on hyperbaric oxygen and blood substitutes to transport oxygen into tumors or in situ generation of O2from the tumor microenvironment endogenous H2O2have been explored to relieve the tumor hypoxia and to improve therapeutic efficiency.In addi-tion,it is potential to design hypoxia-responsive nanocarriers based on tumor hypoxia microenvironment to deliver anticancer drugs to the targeted tumor site,thereby improve drug concentrations in targeted site,significantly increase the antitumor efficiency and reduce the side-effects of drugs.This review gives an overview of the advances in relieving tumor hypoxia and hypoxia-responsive nanocarriers for tumor to provide a reference for the research and development of new antitumor drugs.