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Tumor recurrence caused by metastasis is a major cause of death for patients.

The combination of therapeutic and diagnostic functions in a single platform has aroused great interest due to the more optimal synergistic effects that can be obtained as compared to any single theranostic approach alone. However, current nanotheranostics are normally formed via complicated construction steps involving the pre-synthesis of each component and further conjugation via chemical bonds, which may cause low integration efficiency and limit production and applications. Herein, a tumor-targeting and tumor-responsive all-in-one nanoplatform based on mesoporous silica nanocarriers (MSNs) was fabricated via a facile approach utilizing efficient and nondestructive physical interactions for long-wavelength fluorescence imaging-guided synergistic chemo-catalytic-photothermal tumor therapy. The MSNs were endowed with these multimodal theranostics via a simple hydrothermal method after coordinating with Fe2+ and glutathione (GSH) to introduce ferroferric oxide and carbon dots in situ. The former acts as a photothermal agent and catalytic agent to generate local heat under 808 nm irradiation and also when toxic hydroxyl radicals (˙OH) are in contact with abundant hydrogen peroxide in cancer cells, while the latter participates in fluorescence imaging. After loading with paclitaxel (PTX), polyester and folic-acid-conjugated cyclodextrin were employed to serve as an esterase-sensitive gatekeeper controlling PTX release from the MSN pores and as a tumor-targeting agent for accurate therapy, respectively. As expected, the nanoplatform was efficiently taken up by tumor cells over healthy cells, and then, synergetic chemo-catalytic-photothermal therapy was performed, resulting in 5-fold greater apoptosis of tumor cells as compared to healthy cells under 808 nm irradiation. Moreover, in vivo data from tumor-bearing mouse models showed that tumors were significantly inhibited, and the survival rates of these mice increased to greater than 80% after 5 weeks of treatment with our nanoplatform. These therapeutic processes could be directly tracked via fluorescence imaging enabled by carbon dots and, therefore, our nanoplatform provides a promising theranostics approach for tumor treatment.

Herein, a rambutan-like nanocomplex (PDA-SNO-GA-HA-DOX, PSGHD for short) was designed to enable effective and accurate tumor therapy. The PSGHD nanocomplex consists of an S-nitrosothiol-functionalized polydopamine (PDA-SNO) core and a gambogic acid-derivatized hyaluronic acid (HA-GA) shell with doxorubicin (DOX) as the cargo. Due to the HA section, the PSGHD nanocomplex can be rapidly and selectively internalized by tumor cells instead of healthy cells in 12 h of co-incubation. After that, the internalized PSGHD nanocomplex is able to gradually release both DOX (agent for chemotherapy) and GA (agent for enhancing thermal damage) under different tumor-specific physiological conditions (low pH and rich HAase). When 808 nm NIR radiation was employed, the PSGHD nanocomplex further demonstrated excellent photothermal conversion to increase the local temperature over 43 °C and convert SNO to nitric oxide (NO, an agent for decreasing drug-efflux). Based on the synergistic effects of NO/DOX and GA/heat, the PSGHD nanocomplex simultaneously achieved tumor-specific low-drug-efflux chemotherapy and low-temperature photothermal therapy, resulting in an eight-fold apoptosis of tumor cells over normal cells under NIR radiation. In vivo data from mouse models further showed that the PSGHD nanocomplex can completely inhibit tumor growth and significantly prolong the survival rate of tumor bearing mice in 50 days, demonstrating the high efficiency of the PSGHD nanocomplex for tumor therapy.

Herein, we reveal a double emulsion method combining the sol-gel method to prepare poly(lactic-co-glycolic acid) microspheres with different porous structures for sequential release of two types of biomolecules. By controlling the ripening time of the emulsion, multiple interconnected chambers could be easily chosen to be either embedded in microspheres or opened to the surface. These two types of microspheres exhibited different kinetics for the release of both small molecules and proteins, where the release from microspheres with open pores (5 day over 90%) was much faster than the release from microspheres with embedded pores (25 day over 90%). After loading with interleukin-4 (IL-4) and melatonin, these microspheres were further encapsulated in a sodium alginate hydrogel to form a patch for cutaneous regeneration. The prepared patch was able to recruit alternatively activated (M2) macrophages in the early stage (fast release of IL-4) and promote the growth of blood vessels in the long term (slow release of melatonin), resulting in significantly enhanced cutaneous regeneration. These results also demonstrate the potential of this novel delivery system to deliver multiple therapeutics and achieve synergistic effects.