Although notable progress has been made on novel cancer treatments, the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients. Chemoimmunotherapy, combining chemotherapeutics and immunotherapeutic drugs, has emerged as a promising approach for cancer treatment, with the advantages of cooperating two kinds of treatment mechanism, reducing the dosage of the drug and enhancing therapeutic effect. Moreover, nano-based drug delivery system (NDDS) was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery, tumor microenvironment response and site-specific release. Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations, such as liposomes (Doxil^®, Lipusu^®), nanoparticles (Abraxane^®) and micelles (Genexol-PM^®). The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment, which could greatly enhance the therapeutic efficacy, reduce the side effects and optimize the clinical outcomes of cancer patients. Herein, the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed, and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.

Docetaxel has been recognized as one of the most efficient anticancer drugs over the past decade; however, its poor water solubility and systemic toxicity have greatly limited its clinical application. In recent decades, the emergence of nanotechnology has provided new drug delivery systems for docetaxel, which can improve its water solubility, minimize the side effects and increase the tumor-targeting distribution by passive or active targeting. This review focuses on the research progress in nanoformulations related to docetaxel delivery – such as polymer-based, lipid-based, and lipid-polymer hybrid nanocarriers, as well as inorganic nanoparticles – addressing their structures, characteristics, preparation, physicochemical properties, methods by which drugs are loaded into them, and their in vitro and in vivo efficacies. Further, the targeted ligands used in the docetaxel nanoformulations, such as monoclonal antibodies, peptides, folic acid, transferrin, aptamers and hyaluronic acid, are described. The issues to overcome before docetaxel nanoformulations can be used in clinical and commercial applications are also discussed.

A multifunctional pH-sensitive polymeric nanoparticle system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy. The nanoparticles were self-assembled using the multi-block polymer poly(lactic acid)-poly(ethylene glycol)-poly(L-lysine)-diethylenetriamine pentaacetic acid (PLA-PEG-PLL-DTPA) and the pH-sensitive material poly(L-histidine)-poly(ethylene glycol)-biotin (PLH-PEG-biotin). The anti-hepatocellular carcinoma (HCC) drug sorafenib was encapsulated inside the nanoparticles. Gd ions were chelated to the DTPA groups which were distributed on the nanoparticle surface. Biotinylated vascular endothelial growth factor receptor (VEGFR) antibodies were linked to the surface biotin groups of nanoparticles through the avidin linker to form the target pH-sensitive theranostic nanoparticles (TPTN). TPTN exhibited spherical or ellipsoidal shapes, uniform particle size distribution (181.4 ± 3.4 nm), positive zeta potential (14.95 ± 0.60 mV), high encapsulation efficiency (95.02 ± 1.47%) and drug loading (2.38 ± 0.04%). The pH-sensitive sorafenib release from TPTN was observed under different pH values (47.81% at pH = 7.4 and 99.32% at pH = 5.0, respectively). In cell cytotoxicity studies, TPTN showed similar antitumor effect against HepG2 cells compared to solubilized sorafenib solution after pre-incubation in acid PBS (pH = 5.0) for 1 h in vitro (P > 0.05). In in vivo anti-tumor studies, TPTN showed significantly higher antitumor effect in H22 tumor (VEGFR overexpressed cell line) bearing mice compared to the solubilized sorafenib solution (oral or i.v. administration) group (P < 0.05). In the MRI test, the T₁ relaxivity value of TPTN was 17.300 mM⁻¹ s⁻¹ which was 3.6 times higher than Magnevist® (r1 = 4.8 mM⁻¹ s⁻¹). As a positive contrast agent, TPTN exhibited higher resolution and longer imaging time (more than 90 min) in the MRI diagnosis of tumor-bearing mice compared to Magnevist® (more than 60 min). Furthermore, histological examination of TBN (blank TPTN, without sorafenib loaded) showed no visible tissue toxicity compared to normal saline. Thus, TPTN possessed dual-loading drugs and imaging agents, active targeting and pH-triggered drug release properties in one platform with good biocompatibility. All of these results indicated that TPTN was a promising theranostic carrier which could be a platform for the development of novel multifunctional theranostic agents.

In this work, novel docetaxel (DTX) -loaded Tween 80-free Pluronic P123 (P123) micelles with improved therapeutic effect were developed. The freeze-dried DTX-loaded P123 micelles (DTX-micelles) were analyzed by HPLC, TEM and DLS to determine the DTX loading, micelle morphology, size, respectively. The in vitro cytotoxic activity of DTX-micelles in HepG2, A549 and malignant melanoma B16 cells were evaluated by MTT assay. The corresponding in vivo antitumor efficacy was assessed in Kunming mice bearing B16 tumor after intravenous administration. The DTX-loading and efficiency into the micelles were 2.12 ± 0.09% and 86.34 ± 3.32%, respectively. The DTX-micelles were spherical with a mean particle size of 50.7 nm and size distribution from 22 to 84 nm, which suggested that they should be able to selectively accumulate in solid tumors by means of EPR effect, with a zeta potential of −12.45 ± 3.24 mV. The in vitro release behavior of DTX from DTX-micelles followed the Weibull equation. Compared with Duopafei^®, DTX-micelles showed higher cytotoxicity against HepG2 (P < 0.01), A549 (P < 0.05) and B16 (P < 0.01) cells. In addition, DTX-micelles exhibited remarkable antitumor activity and reduced toxicity on B16 tumor in vivo. The tumor inhibition rates (TIR) of DTX-micelles was 91.6% versus 76.3% of Duopafei^® (P < 0.01). These results suggested that P123 micelles might be considered as an effective DTX delivery system.