Introduction

Nanoparticle-based drugs delivery system for disease treatment can enhance drugs accumulation at the lesion sites through retention and permeability effect, which can overcome complex biological environment to enhance therapeutic effects and avoid unnecessary side effects [1, 2]. However, considerable efforts have been devoted to nanoparticles. The exploitation of nanoparticles with optimized properties still have some challenges, such as post-nanoparticles entry to the blood circulation. This can be easily eliminated by the liver, spleen, reticuloendothelial system, and body immune system, resulting in a short half-life time, and limited nanoparticles accumulated at the lesion sites [3, 4].

Although the development of nanoengineering and modifying biomaterials on the surface of nanoparticles have achieved remarkable progress, the unanticipated material properties can negatively influence the function of nanoparticles in physiologically relevant systems [5, 6]. Thus, targeting ability, stability and biocompatibility are the three basic elements for the ideal nanoparticle. In recent years, a new type of bionic nanoparticle has been composited by the biologically derived cell membrane (versus cells and vesicles) coated nanoparticles cores, which can surpass the limit of the traditional surface modification approach [7]. Cell membrane biomimetic nanoparticles provide a top-down method to design a multifunctional drug delivery system. This is done by utilizing the complexity and versatility of the cell membrane to cloak nanoparticles and transfer the inherent characteristic of the cell membrane to the surface of the nanoparticle to execute a particular function [8].

As an effective and simple biomimetic strategy, cell membrane camouflaged nanoparticles can keep their membrane structure and antigens and realize special functions, including prolonging blood circulation time, immune escape, and specific recognition [9,10,

Cancer Cell Membrane Biomimetic Nanoparticles

Erythrocyte membranes undergo cloaking to prolong nanoparticles in the blood circulation time, however do not have any targeting ability against cancer cells [28, 29]. To date, some approaches have been made to improve the targeting ability by surface decoration with targeting molecules. These fabricate progress are complicated, and surface modifications can activate the body's immune system to some extent [30,31,32].

More evidence illustrates that cancer cells have unique targeting delivery and immune escape ability due to homologous cancer cells easy aggregation and interaction with the receptor and molecular (galectin-3, the endothelium-expressed β-galactoside-binding protein, tumor-associated Thomsen-Frieden Reich glycoantigen) on the surface of cancer cells [33, 34]. Cancer cells exhibit strong cell–cell communication and escape immune attack ability in the blood based on these merits. Thus, cancer cell membrane (CCM) biomimetic nanoparticles can select accumulation and longer retention at the tumor areas based on the homologous targeting.

As Fig. 2a shows, Chen et al. fabricated a core–shell indocyanine green (ICG) loading and cancer cell membrane cloaking nanoparticle (ICNPs) for theragnostic cancer nanoplatforms [35]. MCF-7 cells were incubated with ICNPs, ICG, and INPs (ICG/poly(lactic-co-glycolic acid)) for 2 h. A stronger fluorescence signal was detected in the cellular cytoplasm of the ICNPs group than in the other two groups. ICNPs were injected into the tumor-carrying nude mice to investigate biodistribution. Most ICNPs were accumulated at the tumor areas via homologous targeting. Only a small amount of ICNPs was detected in the kidney and liver due to MCF-7 cell membrane can disguise ICNPs as cells to decrease kidney and liver interception. ICNPs have high spatial resolution, deep penetration, and real-time dual-modal image monitoring, completely eradicating tumors without tumor relapse upon the combination with near-infrared light irradiation. The survival rate was 100% after 18 days of therapy.

Fig. 2
figure 2

a Illustration of the cancer cell membrane-biomimetic ICNPs nanoparticles for targeting recognition of source cancer cell, dual-modal imaging, and photothermal therapy [35]. Copyright 2016 American Chemical Society. b Schematic illustration of aMMTm preparation and proposed combination therapy of PDT and antiangiogenesis [37]. Copyright 2019 WILEY–VCH Verlag GmbH & Co. KGaA, Weinheim

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Besides, cancer cells generate high levels of glutathione (GSH), consuming ROS during PDT therapy and compromise cancer therapy outcomes [36]. Thus, ameliorating the tumor microenvironment to improve therapy efficiency should be a powerful approach for tumor therapy. As Fig. 2b shows, Min and his co-workers developed porphyrinic zirconyl-based MOFs nanoparticles, loading vascular endothelial growth factor receptor 2 inhibitor apatinib and wrapped with MnO2 to neutralize the intratumorally high levels of GSH. The surface was further coated with a 4T1 cancer cell membrane (aMMTm) [37]. After intravenous injection, aMMTm had longer blood half-time and accumulated at the tumor area via homotypic targeting. MnO2, as to reduce agent scavenger, can consume high levels of GSH at the tumor areas to enhance PDT outcomes. The reaction product Mn2+ can be used as a magnetic resonance imaging contrast agent to detect antiangiogenic drug delivery and distribution in vivo. The obtained multifunctional aMMTm nanosystem combined PDT can significantly enhance tumor outcomes and prolong the survival rate of 4T1 bearing mice.

The CCM biomimetic approach provides a novel strategy to achieve great progress in cancer therapy. However, the CCM biomimetic approach has some shortcomings at the early stage, including the requirements of homologous cancer cells for incubation and prolonged time and post-progressing to obtain CCM. Although CCM biomimetic nanoparticles have some drawbacks, l believe CCM biomimetic nanoparticles are a simple and efficient approach to construct an ideal drug delivery system for cancer treatment in the future.

Platelet Mimicking Nanoparticles

Platelet originates from the cytoplasm of megakaryocytes. The surface of the platelet membrane expressed CD47, can inhibit immune elimination by the body’s immune system and prolong their circulation time in the body’s blood [38,39,40]. Moreover, platelet plays an important role in tumor metastasis, bacterial infection, thrombogenesis, immune escape, and other functions, due to the surface of platelet membrane having unique receptors, antigens, and proteins, such as CD59, P-selection, CD55, and glycoprotein (GP) Ib [41,42,43,44,45]. Thus, platelet membrane (PM) biomimetic nanoparticles can target delivery to injured vascular areas, surrounding and aggregating the tumor cells, due to the surface of PM retaining the integrity of various biomolecules. This can mediate a series of molecular interactions and promote their affinity between tumor cells and platelet membranes [46, 47].

As Fig. 3a shows, Hu et al. developed PM camouflaged core–shell nano vehicle (PM-NV), the nanogel core used to load drugs. The surface of PM was further decorated with protein drugs, which can achieve targeting delivery and site-specific releasing behavior [48]. Tumor necnosis factor-related apoptosis-inducing ligand (TRAIL) and doxorubicin (DOX) as the most important extracellular activators of apoptosis, were simultaneously incorporated into PM-NV (TRAIL-DOX-PM-NV) for tumor therapy. TRAIL-DOX-PM-NV can be endocytosed and digested after incubating with tumor cells, promoting DOX accumulation at the nuclei and improve tumor cell apoptosis. When administered into the tumor mice model, TRAIL-DOX-PM-NV has blood stability, targeting delivery, and immune escape ability, which can aggregate the tumor cells to inhibit cancer cell metastatic and enhance tumor therapy.

Fig. 3
figure 3

a Schematic design of drug-loaded PM-NV for targeting and sequential drug delivery [48]. Copyright 2016 Adv. Mater. b Schematic design of engineering biomimetic nanocarrier for pH-responsive drug delivery and enhanced anti-tumor activity [49]. Copyright 2019 WILEY–VCH Verlag GmbH & Co. KGaA, Weinheim

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After the platelet membrane is fused with other membranes, the obtained products inherit the function of the platelet membrane and retain the advantages of other membranes. As Fig. 3b shows, Liu and his co-workers designed a novel platelet membrane-lipid hybrid biomimetic pH-responsive nanoparticles (PEOz-liposome-DOX) to target delivery and accelerate drug release at tumor acidic environment [49]. During platelet membranes and the liposome fusion process, pH-sensitive lipid DSPE (1,2-dioleoyl-sn-glycero-3-phosphoethaNolamine)-PEOz and DOX were simultaneously incorporated into the hybrid membrane carrier, accelerating drug-release at acidic conditions. In mouse tumor models, PEOz-liposome-DOX nanoplatform significantly exhibited tumor accumulation capacity, longer half-time, and excellent anti-tumor effects compared to traditional nanoparticles without pH-responsive or traditional liposomes with pH-sensitive behavior.

Platelet membrane biomimetic camouflage nanoparticles have stealthy and biofriendly behavior in the blood circulation, reducing cell uptake by macrophage cells, selective adhesion to damage vasculatures, and improved nanoparticles adherence to cancer cells or pathogens to improve therapy effect.

Lymphocyte Biomimetic Nanoparticles

Lymphocytes, including T cells, B cells, and NK cells as the typical immune cells, play a core role in the intrinsic immune system against pathogen infection and tumor progression [49]. The number of lymphocytes increases rapidly after being activated by various diseases, and have far longer half-time’s in the blood circulation [65]. However, the application and investigation of biomimetic nanoparticles are still at an infant stage. There exist various challenges and problems that need to be solved, including the source of the cell membrane, the fabrication process of biomimetic nanoparticles, and the safety, biocompatibility, targeting ability of these biomimetic nanoparticles in tumor therapy.

Different cell membranes have different sources, such as erythrocytes and platelets, which come from the body's common and abundant blood cells where they can be easily obtained [66]. Tumor cell membrane and immune cell membranes however, require tedious fabrication process, including large samples, cultivation, and amplification in vitro [67]. Biomimetic nanoparticles as foreign materials can induce a robust immune response after injection into the body. Therefore, design and construction of homologous cell membrane-based biomimetic nanoparticles origin from the patients’ lesion areas should be considered.

Uneven or incomplete coverage of nanoparticles may easily induce the body’s immune response to eliminate the biomimetic nanoparticles system. Thus, kee** the integrity of the cell membrane structure is an important problem to be considered during the fusion and extraction process [68]. At present, repeating the freeze–thaw process and the hypotonic treatment is the most common extraction approach to maintain the cell membrane's functions and integrity [69]. However, these current processes are still stagnant at the early research stage, which require more time and procedures to optimize until they meet the clinical applications.

Safety and biocompatibility are the most important factors before approval for clinical application. Currently, cell membrane biomimetic technology exhibits good biocompatibility and targeting ability compared to other traditional modified methods. However, these trials are still staying at a simple and primary mice experiment, which require more in vivo detail experiments and information to illustrate.

Above all, cell membrane biomimetic nanoparticles exhibit superior tumor therapy effects after being combined with the advantages of cell membrane and nanoparticles. After cell membranes are modified with targeting molecules and integrated with nanoparticles or other therapeutic agents, biomimetic nanoparticles can realize excellent tumor therapy outcomes. However, these works are still at the early stage, which require repeatability experimentation before clinical use.

Conclusion

In summary, the cell membrane biomimetic approach has made a great contribution to tumor therapy. This article summarizes some types of cell membrane (erythrocyte membrane, cancer cell membrane, platelet membrane, and leukomonocyte membrane) biomimetic nanoparticles to endow them with longer blood circulation time, immune escape, and tumor targeting ability to realize favorable anti-tumor effects. However, the clinical application of biomimetic nanoparticles encounters many challenges to resolve, including complex fabrication process, unsuitable large-scale production, low yields, and difficult preservation. Overall, targeting delivery, excellent anti-tumor properties, prolonged circulation time, minimal side effects, and positive economic effects should be the elemental factors of the cell membrane biomimetic approach for translating into clinical utilization.