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It is important for antitumor drugs to accumulate at the tumor site and penetrate deeply to play a role in treatment. However, it is difficult for the drugs to reach the destination on account of the complex tumor microenvironment such as elevated tumor interstitial fluid pressure (IFP) and solid stress. Here, we report a type of nanocarrier composed entirely of Camellia oleiferaprotein (COP), which could lower tumor IFP and solid stress. Its physicochemical properties, cellular uptake, in vitrocytotoxicity and tumor perfusion, biodistribution, and in vivoantitumor efficiency were evaluated. It was found that COP NPs had good cellular uptake ability and cytocompatibility. When loading doxorubicin, COP NPs showed an in vitroconcentration-dependent cytotoxicity. Importantly, the tumor IFP and solid stress were greatly reduced after injecting COP NPs into tumor-bearing mice, leading to more drug accumulating in the tumor and a longer survival time for tumor-bearing mice. Therefore, our study provided a new strategy to improve the tumor microenvironment and to achieve better antitumor efficiency.

A class of new dendritic phospholipid compounds with different hydrophilic dendritic poly(l-lysine) peripheries from generations 1 (G1) to 3 (G3) (DPL-1 to DPL-3) were synthesised and nano-drug delivery systems based on these compounds were prepared (DPN-2 and DPN-3). DPL-1 couldn't self-assemble into nanocarriers. The size, TEM image, and the CD spectrum of DPN-2 and DPN-3 were experimentally examined. The effect of the peripheral structure of dendritic phospholipid-based nanocarriers on their biological performance and drug delivery efficiency was studied. In vitrocytotoxicity studies demonstrated that the DOX-loaded DPN-3 shows higher cytotoxicity against 4T1 cells and BGC823 cells than DPN-2. DOX-loaded DPN-3 also showed excellent behaviours in cell internalization and 4T1 multicellular spheroid penetration. The composition of the hydrophilic block in dendritic phospholipids affected the self-assembly behaviour, properties and delivery efficiency of the formed nanocarriers. This work will be helpful for building drug delivery systems with characteristics of high delivery efficiency and low cytotoxicity for clinical applications.