The main traditional cancer treatment methods include surgical treatment, chemotherapy and radiotherapy. Surgical treatment can only treat patients with early-stage tumors whose cancer cells have not yet metastasized. Chemotherapy lacks selectivity between cancer cells and normal cells. Radiotherapy can only eliminate undifferentiated tumors, and radiation causes serious side-effects [1], [2], [3]. It is difficult to eliminate tumor cells without damaging normal human cells. The emergence of nanomaterials may offer a solution to this problem[4], [5]. The small size, surface, volume and quantum effects, and the unique acoustic, electrical, optical, magnetic and thermal characteristics of nanomaterials provide the basis for the diagnosis and treatment of tumors [6], [7], [8], [9].

The ideal tumor DDS is safe and non-toxic, and has targeting ability to tumor sites and controllable drug release[10], [11]. Common drug carriers include liposomes, macromolecules, microparticles. As exogenous substances of organisms, most drug carriers are easily recognized and cleared by the immune system and the liver and kidney detoxification system, which brings great challenges to drug delivery[12]. Both passive and active targeting are limited by uncontrollable factors such as tumor tissue vascular differentiation and penetration at different stages, surface receptor distribution density, and ligand receptor recognition targeting efficiency being easily affected in the preparation of nanomaterials[13], [14]. Development of nanomaterials with good biocompatibility, high drug loading capability and strong targeting capability as a DDS in the field of tumor therapy is therefore urgent.

At present, drug carriers with good biocompatibility have attracted more attention, such as red blood cell carriers and cell membrane biomimetic carriers, and a new DDS based on CCM has attracted much attention in recent years[15], [16]. Compared with traditional drug carriers, CCM biomimetic carries have unique advantages: 1) good biocompatibility. One of the reasons why tumor cells proliferate in the body rapidly and in large quantities is that tumor cells have good biocompatibility[17]. Loading drugs with CCMs can effectively reduce the immune response of drugs[18]; 2) The CCM can be extruded and deformed, and smoothly pass through biofilm pores smaller than its own particle size[19], [20]; 3) Prolonging the half-life and preventing the DDS from being recognized and phagocytized by reticuloendothelial system, thus prolonging the circulation time of drugs in the body and maintaining the stability of blood drug concentration[21], [22]; 4) Homologous targeting, i.e. the CCM has homologous binding capability with membrane proteins between cells so as to recognize tumor tissues in vivo and carry out tumor targeting by homologous cell membrane protein adhesion[15], [23], [24]. However, the drug loading capacity of the cell membrane is limited, and drug loading through the osmotic pressure difference can easily cause membrane surface protein denaturation, which will damage the targeting and immune escape effect of CCMs.

The composition of liposomes is similar to that of cell membranes, and are also self-assembled by phospholipid and cholesterol. A phospholipid is composed of polar phospholipid head groups and hydrophobic lipid tails. In water, the hydrophobic tails self-position to form a spherical structure with water at the center, surrounded by a lipophilic bilayer membrane[25]. Liposomes have the advantages of good biocompatibility, low toxicity, high loading capacity and controllable release kinetics, which make them suitable drug carriers[26], [27]. However, liposomes are prone to inducing an immune response, and as an exogenous substance of organisms, liposomes are easily recognized and cleared by the reticuloendothelial system and the liver and kidney detoxification system. This reduces the efficacy of anti-tumor drugs, leads to the failure of cancer therapy and has other toxic side effects[28]. With the advance of liposome research, the scope of liposome drug loading is also increasing, broadening its prospects in the future.

Studies of tumor blood vessels have found that the surface of new blood vessels in tumor tissue is highly expressed with ανβ3 receptors. The RGD sequence and ανβ 3 receptors have binding specificity and high affinity. Therefore, RGD can be coupled with nanoparticles to improve the tumor targeting of the nanoparticle DDS[29], [30]. A proliferation of evidence shows that cancer cells have immune escape and homologous adhesion characteristics due to the existence of a variety of membrane antigens on the surface of the CCMs[1], [31], [32]. This discovery should allow the construction of an ideal nano DDS that has highly tumor-specific affinity and efficient tumor treatment by encapsulating liposomes with the membrane of homologous cancer cells to achieve high-efficiency drug delivery and tumor targeting.

Our research group has conducted extensive research on RGD targeted DDSs and CCM encapsulated nanoparticles DDSs in the early stage[33], [34], [35], [36], [37]. Based on the previous research, we constructed a “shell-core” DDS with high drug loading, active and homologous dual targeting, and long-term blood circulating and immune escaping characteristics, where the cyclic peptide RGD modified CCM was used as the “shell” and drug loaded liposome was used as the “core”. Through in vivo and in vitro experiments, the tumor targeting, drug loading and immune escape characteristics of the DDS were investigated. Glioma cells and tumor bearing Balb/c mice were selected as tumor models to investigate whether the DDS could better inhibit tumor growth. This study lays a foundation for the clinical application of precise targeted therapy for cancer.