Cancer Cell Membrane-Coated Nanoparticles for Cancer Management

Abstract

Cancer is a global health problem in need of transformative treatment solutions for improved patient outcomes. Many conventional treatments prove ineffective and produce undesirable side effects because they are incapable of targeting only cancer cells within tumors and metastases post administration. There is a desperate need for targeted therapies that can maximize treatment success and minimize toxicity. Nanoparticles (NPs) with tunable physicochemical properties have potential to meet the need for high precision cancer therapies. At the forefront of nanomedicine is biomimetic nanotechnology, which hides NPs from the immune system and provides superior targeting capabilities by cloaking NPs in cell-derived membranes. Cancer cell membranes expressing "markers of self" and "self-recognition molecules" can be removed from cancer cells and wrapped around a variety of NPs, providing homotypic targeting and circumventing the challenge of synthetically replicating natural cell surfaces. Compared to unwrapped NPs, cancer cell membrane-wrapped NPs (CCNPs) provide reduced accumulation in healthy tissues and higher accumulation in tumors and metastases. The unique biointerfacing capabilities of CCNPs enable their use as targeted nanovehicles for enhanced drug delivery, localized phototherapy, intensified imaging, or more potent immunotherapy. This review summarizes the state-of-the-art in CCNP technology and provides insight to the path forward for clinical implementation.

Biomimetic cancer cell membrane-coated nanosystems as next-generation cancer therapies

“…The CCM-NS preparation involves: (1) membrane extraction and membrane vesicles isolation; (2) preparation of the nanoparticle core, and (3) fusion of the nanoparticle core with the CCM vesicles [3,5]. Several methods for preparing CCM-NS have been reported so far.…”

“…The size of the vesicles can be tailored and optimized using membrane extrusion. The coating of nanoparticle cores can be carried out by either a coextrusion or sonication process, thus assembling CCM-NS [5].…”

“…The versatility of the nanoparticle cores -both in composition and features -enables the encapsulation of a variety of CONTACT Ana Cláudia Santos, acsantos@ff.uc.pt Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal compounds (drugs, nucleic acids, photosensitizers, imaging components), aiming at cancer therapy and cancer theranostics ( Figure 1) [2,5]. So far, several chemotherapy drugs (e.g., doxorubicin, paclitaxel, camptothecin, cisplatin) have been successfully guided to malignant lesions by CCM-NS with improved anticancer effects when compared to non-coated counterparts [1,2,5,6]. The augmented performance is ascribed to: (1) improved targeted drug delivery and (2) enhanced cellular uptake, resulting from homotypic binding features of surface cell adhesion components, which favors (3) sitespecific accumulation in cancer tissues, also aided by (4) prolonged blood circulation time.…”

“…The applicability of CCM-NS as highly-specific biomimetic anticancer nanovaccines is underpinned by the natural immunogenicity imparted by the surface exposition of cancerspecific antigens [6]. The coated nanoparticle core can function as a drug or immunoadjuvant reservoir to extend the cancer vaccine potential by boosting immune responses [5,6]. Particularly, imiquimod -loaded PLGA nanoparticles were coated with mannose-decorated murine melanoma cell membrane (B16-OVA cell) for improved antigen presenting cells (APCs) targeting.…”

“…Cell membrane-coated nanosystems consisting of biomimetic attributes can maximize drug targeting by exploiting the inherited biofunctionalities of cell membranes extracted from source cells [2]. Particularly, cancer cell membrane (CCM) coatings preserve the source targeting abilities imparted by a repertoire of cell adhesion molecules, providing CCM-coated nanosystems (CCM-NS) with additional cancer-homing features via a homotypic targeting mechanism [5]. Additionally, the molecularly rich surface of CCM coatings enable surface exposition of cancer-specific antigens, capable of eliciting multiantigen responses with relevant applications in anticancer vaccination and immunotherapy [5,6].…”