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Mesoporoussilica nanoparticles (MSNs) are promising solid supportsfor controlled anticancer drug delivery. Herein, we report biocompatiblelayer-by-layer (LbL) coated MSNs (LbL-MSNs) that are designed andcrafted to release encapsulated anticancer drugs, e.g., doxorubicinhydrochloride (DOX), by changing the pH or by adding competitive agents.The LbL coating process comprises bis-aminated poly(glycerol methacrylate)s(BA-PGOHMAs) and cucurbit[7]uril (CB[7]), where CB[7] serves as amolecular bridge holding two different bis-aminated polymeric layerstogether by means of host–guest interactions. This integratednanosystem is tuned to respond under specific acidic conditions orby adding adamantaneamine hydrochloride (AH), attributed to the competitivebinding of hydronium ions or AH to CB[7] with BA-PGOHMAs. These LbL-MSNhybrids possess excellent biostability, negligible premature drugleakage at pH 7.4, and exceptional stimuli-responsive drug releaseperformance. The pore sizes of the MSNs and bis-aminated compounds(different carbon numbers) of BA-PGOHMAs have been optimized to provideeffective integrated nanosystems for the loading and release of DOX.Significantly, the operating pH for the controlled release of DOXmatches the acidifying endosomal compartments of HeLa cancer cells,suggesting that these hybrid nanosystems are good candidates for autonomousanticancer drug nanocarriers actuated by intracellular pH changeswithout any invasive external stimuli. The successful cellular uptakeand release of cargo, e.g., propidium iodide (PI), in human breastcancer cell line MDA-231 from PI-loaded LbL-MSNs have been confirmedby confocal laser scanning microscopy (CLSM), while the cytotoxicitiesof DOX-loaded LbL-MSNs have been quantified by the Cell Counting Kit-8(CCK-8) viability assay against HeLa cell lines and fibroblast L929cell lines. The uptake of DOX-loaded LbL-MSNs by macrophages can beefficiently reduced by adding biocompatible hydrophilic poly(ethyleneglycol) or CB[7] without destroying the capping. In vivo tumor-growthinhibition experiments with BALB/c nude mice demonstrated a highlyefficient tumor-growth inhibition rate of DOX-loaded LbL-MSNs, suggestingthat the novel type of LbL-MSN materials hold great potentials inanticancer drug delivery. [ABSTRACT FROM AUTHOR]

Combinations of different therapeutic strategies, including chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT), are needed to effectively address evolving drug resistance and the adverse effects of traditional cancer treatment. Herein, a camouflage composite nanoformulation (TCBG@PR), an antitumor agent (tubercidin, Tub) loaded into Cu-doped bioactive glasses (CBGs) and subsequently camouflaged by polydopamine (PDA), and red blood cell membranes (RBCm), was successfully constructed for targeted and synergetic antitumor therapies by combining CT of Tub, CDT of doped copper ions, and PTT of PDA. In addition, the TCBG@PRs composite nanoformulation was camouflaged with a red blood cell membrane (RBCm) to improve biocompatibility, longer blood retention times, and excellent cellular uptake properties. It integrated with long circulation and multimodal synergistic treatment (CT, CDT, and PTT) with the benefit of RBCms to avoid immune clearance for efficient targeted delivery to tumor locations, producing an "all-in-one" nanoplatform. In vivo results showed that the TCBG@PRs composite nanoformulation prolonged blood circulation and improved tumor accumulation. The combination of CT, CDT, and PTT therapies enhanced the antitumor therapeutic activity, and light-triggered drug release reduced systematic toxicity and increased synergistic antitumor effects.