Gliomas are the most common tumor of the central nervous system. However, the presence of the brain barrier blocks the effective delivery of drugs and leads to the treatment failure of various drugs. The development of a nanoparticle drug delivery system (NDDS) can solve this problem. In this review, we summarized the brain barrier (including bloodbrain barrier (BBB), blood-brain tumor barriers (BBTB), brain-cerebrospinal fluid barrier (BCB), and nose-to-brain barrier), NDDS of glioma (such as passive targeting systems, active targeting systems, and environmental responsive targeting systems), and NDDS efficacy improvement strategies and deficiencies. The research prospect of drug-targeted delivery systems for glioma is also discussed.

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Malignant tumors represent some of the most intractable diseases that endanger human health. A glioma is a tumor of the central nervous system that is characterized by severe invasiveness, blurred boundaries between the tumor and surrounding normal tissue, difficult surgical removal, and high recurrence. Moreover, the blood–brain barrier (BBB) and multidrug resistance (MDR) are important factors that contribute to the lack of efficacy of chemotherapy in treating gliomas. A liposome is a biofilm-like drug delivery system with a unique phospholipid bilayer that exhibits high affinities with human tissues/organs (e.g., BBB). After more than five decades of development, classical and engineered liposomes consist of four distinct generations, each with different characteristics: (i) traditional liposomes, (ii) stealth liposomes, (iii) targeting liposomes, and (iv) biomimetic liposomes, which offer a promising approach to promote drugs across the BBB and to reverse MDR. Here, we review the history, preparatory methods, and physicochemical properties of liposomes. Furthermore, we discuss the mechanisms by which liposomes have assisted in the diagnosis and treatment of gliomas, including drug transport across the BBB, inhibition of efflux transporters, reversal of MDR, and induction of immune responses. Finally, we highlight ongoing and future clinical trials and applications toward further developing and testing the efficacies of liposomes in treating gliomas.

Background Effective treatment of glioma requires a nanocarrier that can cross the blood–brain barrier (BBB) to target the tumor lesion. In the current study, elemene (ELE) and cabazitaxel (CTX) liposomes were prepared by conjugating liposomes with transferrin (Tf) and embedding the cell membrane proteins of RG2 glioma cells into liposomes (active-targeting biomimetic liposomes, Tf-ELE/CTX@BLIP), which exhibited effective BBB infiltration to target glioma. Results The findings showed that Tf-ELE/CTX@BLIP was highly stable. The liposomes exhibited highly significant homologous targeting and immune evasion in vitro and a 5.83-fold intake rate compared with classical liposome (ELE/CTX@LIP). Bioluminescence imaging showed increased drug accumulation in the brain and increased tumor penetration of Tf-ELE/CTX@BLIP in orthotopic glioma model nude mice. Findings from in vivo studies indicated that the antitumor effect of the Tf-ELE/CTX@BLIP led to increased survival time and decreased tumor volume in mice. The average tumor fluorescence intensity after intravenous administration of Tf-ELE/CTX@BLIP was 65.2, 12.5, 22.1, 6.6, 2.6, 1.5 times less compared with that of the control, CTX solution, ELE solution, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP groups, respectively. Histopathological analysis showed that Tf-ELE/CTX@BLIP were less toxic compared with administration of the CTX solution. Conclusion These findings indicate that the active-targeting biomimetic liposome, Tf-ELE/CTX@BLIP, is a promising nanoplatform for delivery of drugs to gliomas. Graphic Abstract

Chemotherapeutic agents trigger antitumor immune response through inducing immunogenic tumor cell death. However, severe toxicity to immune system and insufficient immunogenic cell death hinder chemotherapy from arousing efficient antitumor immunity in vivo. In this study, the cytotoxic drug, pirarubicin (THP), was entrapped into nanostructured lipid carriers (NLC); THP-NLC significantly reduced the toxicity of THP to immune system and improved immune status of breast cancer bearing mice. When THP-NLC was coinjected with iRGD (a tumor-penetrating peptide), drug accumulation in tumors was greatly elevated, which led to significant control of tumor growth and increase of immunogenic tumor cell death. Subsequently, the cytotoxic T lymphocytes (CD3 and CD8 cells) infiltration and cytokine (IFN-γ and INF-α) secretion in tumors were heavily increased. The efficient T-cell dependent control of tumors in the late stage and the lower side effects contributed to the longest whole survival of THP-NLC + iRGD treated mice. Therefore, the coadministration of THP-NLC with iRGD resulted in increased tumor cell direct-killing death and enhanced antitumor immune response. Our results illustrated that THP could serve as an immunogenic cell death inducer and the proposed drug delivery strategy might impact cancer immunotherapy by arousing increased immunogenic tumor cell death.