The authors state that "Red blood cell (RBC) hitchhiking is a method of drug delivery that can increase drug concentration in target organs by orders of magnitude." They explain that in RBC hitchhiking, "drug-loaded nanoparticles (NPs) are adsorbed onto red blood cells and then injected intravascularly, which causes the NPs to transfer to cells of the capillaries in the downstream organ." The review notes that "RBC hitchhiking has been demonstrated in multiple species and multiple organs" and has been "successfully employed in numerous preclinical models of disease, ranging from pulmonary embolism to cancer metastasis."

In this Nature Communications article, the authors report that "nanocarriers adsorbed onto red blood cells (RBCs) dramatically increase their accumulation in target organs downstream from the injection site." Using rodent and pig models, they found that RBC-hitchhiking "boosts delivery of nanocarriers to lungs, brain, and other organs by up to an order of magnitude or more compared to free nanocarriers." The study concludes that RBC-hitchhiking "enables high-efficiency vascular delivery" and suggests applications for drugs treating conditions such as "acute lung disease, stroke, and cancer," showing that RBCs can serve as highly effective carriers for therapeutic nanoparticles in vivo.

The authors describe "RBC-mediated delivery of anti-tumor drugs" and note that anthracycline antibiotics, such as doxorubicin and daunorubicin, can spontaneously partition into red blood cells after intravenous administration. They state that "studies both in patients and rats demonstrated that almost 50% of doxorubicin can be found in the RBC compartment after intravenous administration" and that this RBC-associated drug fraction benefits from prolonged circulation and protection from macrophage uptake and organ clearance. The review concludes that erythrocytes loaded with anthracyclines in preclinical models can carry higher doses of doxorubicin, limit cardiac toxicity, and show superior antitumor effects compared with free drug.

This review on red blood cells as vascular drug carriers reports that loading a hydrophobic anti-tumor agent, dequalinium, into mouse RBCs "provided much longer half-life in circulation than PEG-liposomal formulation (5–6 days vs 4 hours)." It further notes that anti-cancer drugs such as doxorubicin have been encapsulated into carrier RBC using various loading schemes and that such RBC carriers can restrict drug toxicity and improve delivery to tumors through mechanisms including antibody targeting and the enhanced permeation and retention (EPR) effect. Pilot studies cited include delivery of cytotoxic agents to malignant cells using microparticles made from RBC ghosts, demonstrating functional anticancer drug transport to target cells in experimental models.

In recent years, significant progress has been made in blood cell-inspired drug delivery strategies, with red blood cells-based (RBCs-based) platforms showing particular promise due to their inherent physiological advantages. Numerous studies … have demonstrated that RBCs can serve as either direct or indirect drug carriers for targeted delivery to various organs including lungs, brain, liver, and spleen, depending on therapeutic requirements. Importantly, for specific disease treatments (e.g., lymphoma, leukemia), RBCs-based delivery systems significantly reduce drug uptake by non-target organs while simultaneously achieving prolonged systemic circulation and enhanced therapeutic efficacy.

The authors describe red blood cells as a "unique drug delivery system" and "supercarriers" capable of enhancing pharmacokinetics and modulating pharmacodynamics for various cargoes, including anticancer agents. They explain that RBC carriage prolongs circulation time, alters distribution between plasma and cells, and often enhances bioavailability, allowing reduced dosage and adverse effects. The review also summarizes industrial and academic efforts moving toward clinical use, and notes that tumor antigens and other cancer-related payloads have reached Phase I/II and Phase II clinical trials when delivered using RBC-based technologies, indicating practical translation beyond in vitro studies.

This Scientific Reports study examines how nanoparticles bind to red blood cells and affect delivery, noting that "RBC-hitchhiking of certain 100 nm polymeric nanoparticles increased their accumulation in lungs up to 120-fold compared to non-hitchhiking controls." The authors show that by tuning nanoparticle size and surface charge, "adsorption to RBCs can be optimized," leading to markedly enhanced localization in downstream organs after intravascular injection. The paper provides quantitative evidence that red blood cells can be used as efficient carriers for nanoparticle-based therapeutics, including potential anticancer drugs, by exploiting this hitchhiking mechanism.

This review states that "Red blood cell-based drug delivery systems have been explored for the delivery of chemotherapeutic agents, enzymes, and other biologics" due to their long circulation time and biocompatibility. It summarizes preclinical and early clinical work in which drugs are either encapsulated inside RBCs or attached to their surface, noting that such systems "can improve pharmacokinetics, reduce toxicity, and increase drug concentration in target tissues." The article highlights applications in oncology, including RBC carriers for anticancer drugs, but emphasizes that most evidence to date comes from animal models and early-phase human studies.

This article describes nanoparticles cloaked with red blood cell membranes as a biomimetic cancer drug delivery platform. The authors explain that RBC membrane-coated nanoparticles "inherit the long circulation and immune evasion properties of native RBCs" and can be loaded with chemotherapeutic agents to enhance tumor targeting. In tumor-bearing animal models, these RBC-mimicking nanocarriers "exhibited prolonged blood retention, increased tumor accumulation, and improved antitumor efficacy compared with conventional nanoparticles," providing experimental evidence that RBC-derived carriers are effective vehicles for anticancer drugs in vivo.

This review focuses on refunctionalization of erythrocyte-based nanomedicine for enhancing cancer-targeted drug delivery. To achieve this, scientists take advantage of erythrocytes (red blood cells; RBCs) as drug carriers and develop RBC membrane (RBCm) coating nanotechnology. These surface functionalization techniques have improved the delivery efficiency of erythrocyte-based nanomedicine in cancer chemotherapy, cancer immunotherapy, cancer photodynamic therapy (PDT)/photothermal therapy (PTT), and their combined therapy… In vitro results showed that this nanotherapy exhibited tumor growth inhibition approximately 6-fold greater than commercial free Taxol and DOX after 21 days… In vivo results revealed that treatment with RBCp exhibited the highest antitumor efficacy by remarkably inhibiting tumor volumes by 90% over 18 days compared to other treatments.

Being biomimetic nanoparticles, [nanoerythrosomes] have enhanced the stability profile of drugs and their excellent site-specific targeting ability makes them potential carrier systems in the diagnosis and therapy of wide variety of tumors including gliomas, lung cancers, breast cancers, colon cancers, gastric cancers, and other solid tumors. Amongst different antineoplastic drugs, methotrexate, etoposide, doxorubicin, and carboplatin have been successfully encapsulated in these carriers previously. For example, drug loaded RBC-membrane coated copper sulphide nanoparticles achieved a 100% melanoma tumor growth inhibition rate in vivo, indicating greatly improved anticancer efficacy compared to conventional formulations.

This article reviews the use of red blood cells and their membranes as carriers for nanodrug delivery systems, including in oncology. It states that RBC-based and RBC membrane–camouflaged nanoparticles combine the "long circulation and immune evasion" characteristics of red cells with the payload capacity of nanocarriers, thereby improving tumor accumulation of drugs via the enhanced permeability and retention effect. The review summarizes multiple in vivo studies where RBC-based nanocarriers delivering anticancer drugs resulted in higher tumor drug concentrations and improved therapeutic outcomes compared with non‑RBC formulations.

In recent years, RBCs-EVs have emerged as an ideal drug delivery platform due to their low immunogenicity and prolonged circulation time in vivo. Studies have shown that drugs loaded into erythrocyte-derived vesicles exhibit enhanced accumulation in tumor tissue and improved antitumor effects compared with free drugs, while simultaneously reducing off-target toxicity. These findings suggest that erythrocyte-based systems can function as effective carriers for chemotherapeutic agents in cancer therapy.

This review says that erythrocytes demonstrate significant potential for revolutionizing drug targeting, especially in cancer therapy. It presents red blood cells as one of several cell-based transporters being investigated for drug delivery.

UC San Diego reports that researchers "developed a novel method of disguising nanoparticles as red blood cells, which will enable them to evade the body’s immune system and deliver cancer-fighting drugs straight to a tumor." The method "involves collecting the membrane from a red blood cell and wrapping it like a powerful camouflaging cloak around a biodegradable polymer nanoparticle stuffed with a cocktail of small molecule drugs." The article notes that red blood cells are "nature’s long-circulation delivery vehicle" and that in mice, "nanoparticles coated in the membranes of red blood cells circulated in the bodies of lab mice for nearly two days," supporting their use as effective carriers for chemotherapy payloads in preclinical cancer models.

The Wyss Institute article describes work where nanoparticles are attached to red blood cells in rodents and reintroduced into the bloodstream, so that "the rodents’ macrophages ignored the nanoparticles and treated the red blood cells normally, allowing them to remain in the blood rather than being cleared by the liver." Later studies showed that when red blood cells were squeezed through capillaries, "the nanoparticles sheared off and got deposited in whatever organ those capillaries happened to be in." In a Nature Communications paper cited here, the team demonstrated that the "hitchhiking" method worked in mice, pigs, and whole human lungs, achieving that "a full 41% of the nanoparticles introduced into blood were deposited into the lung," illustrating the efficiency of RBC-based delivery of nanoparticle drug carriers toward target organs, including tissues relevant to cancer therapy.

Red blood cell-based drug delivery systems, including intact carrier erythrocytes and erythrocyte membrane-coated nanoparticles, have shown promising antitumor efficacy in preclinical models. Encapsulation of chemotherapeutic drugs such as methotrexate and doxorubicin in carrier erythrocytes improved tumor suppression and reduced systemic toxicity when compared with conventional formulations. Although clinical data are still limited, early-phase trials using erythrocyte-based carriers for oncologic indications report acceptable safety profiles and pharmacokinetic advantages.

The indexed biomedical literature includes multiple recent review articles on red blood cell drug delivery in cancer, which suggests the field has enough primary and review evidence to support systematic synthesis.

This technology description explains that "The drug delivery system, 'Red Blood Cell (RBC)-Hitchhiking Nanoparticles' (RHNs), utilizes soft nanoparticles, such as liposomes and nanogels, loaded with drugs and the natural properties of RBCs to target the lung endothelium." Nanoparticles "are adsorbed onto the surface of the RBC and delivered intravascularly," and when RBCs encounter the first capillary bed, "the RBCs are physically squeezed, causing the release of the drug-loaded nanoparticles into the capillary endothelium." The approach is said to "minimize off-target drug effects" and has undergone "validation studies completed in rodent and pig models," indicating robust preclinical evidence that RBCs can effectively carry and release therapeutic drugs, including potential anticancer agents, at target sites.

In this experimental study, nanocarriers loaded with chemotherapeutic agents were adsorbed onto the surface of mouse red blood cells before intravenous injection. The authors report that this "RBC hitchhiking" strategy increased lung tumor accumulation of the nanocarriers by several-fold compared with free nanoparticles, while reducing off‑target distribution. Treatment of tumor-bearing mice with RBC-hitchhiked nanocarriers resulted in significantly inhibited tumor growth and improved survival, demonstrating that RBCs can effectively serve as carriers to enhance delivery of anticancer drugs to tumor sites in vivo.

This review specifically focused on cancer notes that erythrocyte-based systems "offer unique advantages" for anticancer drug delivery, including prolonged circulation, reduced immunogenicity, and the ability to shield cytotoxic drugs from healthy tissues. It summarizes preclinical studies where chemotherapeutic agents such as doxorubicin and paclitaxel were loaded into or onto red blood cells and achieved enhanced antitumor efficacy with decreased systemic toxicity relative to conventional formulations. The article concludes that RBC-based carriers represent a promising platform for cancer therapy, though most evidence to date is from animal models and early-stage clinical investigations.

RBCs can be loaded with antineoplastic agents either by encapsulation or surface coupling and used as circulating depots that slowly release the drug in the bloodstream or deliver it to specific targets. Preclinical oncologic studies have shown that RBC-based formulations of agents such as L-asparaginase, methotrexate, and platinum drugs achieve comparable or superior tumor control with a better safety profile. However, despite promising evidence of efficacy, most RBC-based anticancer products remain in early clinical development and face manufacturing and regulatory challenges.

This review on cell-mediated nanoparticle delivery notes that "only recently have red blood cells been investigated for cellular hitchhiking applications." It explains that by "attaching nanoparticles to the surface of red blood cells" and reinfusing them, the cells can act as carriers that shuttle nanoparticles through the circulation and into target vasculature. The authors discuss how this strategy has been applied for "drug delivery and imaging" and cite studies where RBC-hitchhiking enhanced localization of therapeutic and diagnostic nanoparticles in specific organs, including models relevant to cancer metastasis.

In this preclinical study, chemotherapeutic drugs were encapsulated in red blood cells and administered to tumor-bearing animals. The investigators found that RBC-encapsulated drug formulations led to sustained drug levels in circulation and enhanced accumulation in solid tumors compared with free drug. Moreover, animals receiving the RBC-mediated chemotherapy showed reduced systemic toxicity and improved tumor growth inhibition, supporting the concept that red blood cells can function as effective carriers for anticancer drugs in vivo.

In this study, doxorubicin was noncovalently adsorbed onto the surface of autologous red blood cells to create an RBC-hitchhiking formulation. In mouse models of breast and colon cancer, RBC-hitchhiking doxorubicin produced significantly greater tumor growth delay and survival extension than equivalent doses of free doxorubicin. The improved antitumor efficacy was accompanied by reduced systemic toxicity, indicating that red blood cells can serve as effective carriers for established chemotherapeutic drugs.

Across the nanomedicine literature, red blood cell-based carriers (both intact RBCs used for hitchhiking and RBC membrane-coated nanoparticles) are widely reported to improve circulation time, biodistribution, and tumor or organ-specific accumulation of chemotherapeutic agents in preclinical models. However, as of 2024–2025, these approaches are largely in the preclinical or early clinical stage: most strong evidence comes from rodent and large-animal models, with only limited early-phase trials in humans. This means that there is substantial experimental support that RBCs can effectively carry anticancer drugs, but large-scale clinical proof of improved cancer outcomes in patients remains limited.