Liposomal drug delivery in cancer has moved from a niche concept to a clinical mainstay: today more than a dozen FDA-approved nanocarrier formulations reach patients each year, and lipid nanoparticle (LNP) platforms that proved themselves in COVID-19 mRNA vaccines are now advancing into oncology trials. This article reviews the structural biology of liposomes and LNPs, the diversity of nanoparticle classes entering cancer immunotherapy, and the reagents researchers need to evaluate nanocarrier efficacy in the laboratory.
Liposomes in Cancer Drug Delivery
A liposome is a spherical vesicle bounded by a phospholipid bilayer — the same architecture as a cell membrane. Phospholipids arrange spontaneously into a bilayer in aqueous solution, creating two distinct compartments: an aqueous core that accommodates hydrophilic drugs, and the hydrophobic interior of the bilayer itself, which solubilizes lipophilic molecules. This dual-loading capacity makes liposomes uniquely versatile for combination drug delivery.
The bilayer is typically stabilized with cholesterol, which reduces membrane fluidity and slows drug leakage. Coating the outer surface with polyethylene glycol (PEG) chains — the so-called stealth liposome strategy — sterically shields the vesicle from opsonization by complement proteins and recognition by reticuloendothelial system (RES) macrophages in the liver and spleen, dramatically extending circulation half-life from minutes to many hours (Allen & Cullis, Science 2004).
Passive tumor accumulation occurs via the enhanced permeability and retention (EPR) effect: tumor vasculature is fenestrated (leaky intercellular junctions, pore sizes 200–1,200 nm) and tumor lymphatic drainage is poor, so circulating nanoparticles extravasate and are retained in the interstitium. EPR is a purely passive mechanism — no targeting ligand is required — and it is the pharmacokinetic rationale behind all first-generation liposomal chemotherapeutics (Peer et al., Nat Nanotechnol 2007).
Active targeting overlays a second selectivity layer by conjugating antibodies, nanobodies, peptides, or small-molecule ligands (e.g., folate, transferrin) to the distal terminus of PEG chains, redirecting liposomes to receptors overexpressed on tumor cells or tumor-associated vasculature.
FDA-approved liposomal cancer drugs demonstrate the clinical maturity of the platform:
- Doxil (doxorubicin HCl liposome injection) — the first nanoparticle oncology drug approved by the FDA (November 1995), initially for AIDS-related Kaposi's sarcoma and later extended to ovarian cancer and multiple myeloma.
- DaunoXome (liposomal daunorubicin) — Kaposi's sarcoma.
- Myocet (non-pegylated liposomal doxorubicin) — metastatic breast cancer (EU approval).
- Marqibo (vincristine sulfate liposome injection) — Philadelphia chromosome-negative acute lymphoblastic leukemia.
- Onivyde (liposomal irinotecan) — metastatic pancreatic adenocarcinoma after gemcitabine-based therapy.
Lipid Nanoparticles (LNPs): From mRNA Delivery to Cancer Vaccines
Lipid nanoparticles are structurally distinct from liposomes despite both being lipid-based. A canonical LNP contains four components: an ionizable lipid (e.g., DLin-MC3-DMA, SM-102, ALC-0315), a helper lipid such as DSPC, a PEG-lipid, and cholesterol. Unlike a liposome, an LNP does not have a defined aqueous bilayer; instead it forms an electron-dense lipid core with an inverted micellar interior structure. The ionizable lipid is uncharged at physiological pH — minimizing toxicity during circulation — but becomes protonated in the acidic environment of the endosome, destabilizing the endosomal membrane and enabling cytoplasmic cargo release (Semple et al., Nat Biotechnol 2010). This pH-dependent ionization and superior endosomal escape efficiency is what gives LNPs a higher effective intracellular delivery rate for nucleic acid payloads compared with classical liposomes.
The global deployment of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines — both LNP-formulated — demonstrated that the platform can be manufactured at scale, stored, and administered safely to hundreds of millions of people. This de-risked LNP technology for oncology applications.
In cancer, LNPs are being developed to deliver:
- Tumor-associated antigen mRNA to antigen-presenting cells, inducing cytotoxic T-cell responses.
- Personalized neoantigen mRNA — mutanome-derived sequences unique to each patient's tumor. The leading clinical example is mRNA-4157/V940 (intismeran autogene, Moderna/Merck), an individualized LNP-formulated mRNA vaccine encoding up to 34 tumor neoantigens. As of July 2026, multiple Phase 3 trials are active: INTerpath-001 (high-risk Stage II–IV melanoma, NCT05933577, 1,089 patients enrolled, ACTIVE_NOT_RECRUITING) and INTerpath-002 (resected Stage II–IIIB NSCLC, NCT06077760, RECRUITING).
- CRISPR-Cas9 or base-editor components targeting tumor suppressor restoration or neoantigen expression.
- Immunostimulatory RNA (e.g., circular RNA, self-amplifying RNA) to trigger innate immune cascades within the tumor microenvironment.
Polymeric and Inorganic Nanoparticles in Oncology
Beyond lipid-based carriers, two broad classes of nanoparticles are advancing in cancer research:
Polymeric nanoparticles — PLGA (poly(lactic-co-glycolic acid)) is FDA-GRAS (generally recognized as safe) and biodegrades into lactic acid and glycolic acid, products already present in the body. PLGA nanoparticles are surface-functionalizable and support sustained drug release profiles tunable by polymer molecular weight and lactide-to-glycolide ratio. Related polymers include PLA, PEG-PLA block copolymers (forming polymeric micelles), and chitosan, which carries a natural cationic charge useful for nucleic acid complexation. Active targeting via anti-HER2 scFv, anti-EpCAM antibodies, or folate receptor ligands redirects polymeric carriers to specific tumor subtypes (Shi et al., Nat Rev Cancer 2017).
Inorganic nanoparticles offer unique physical properties not available from lipid or polymer platforms:
- Superparamagnetic iron oxide nanoparticles (SPIONs) — MRI contrast agents and hyperthermia mediators; ferromagnetic heating under alternating magnetic fields kills tumor cells directly.
- Gold nanoparticles (AuNPs) — plasmonic resonance enables photothermal therapy (PTT); surface chemistry is highly versatile for ligand conjugation.
- Mesoporous silica nanoparticles (MSNs) — very high drug loading capacity due to large surface area (up to 1,000 m² g⁻¹) and tunable pore size.
A key pharmacokinetic consideration for all nanoparticle classes is size-dependent biodistribution. Particles below 8 nm are cleared renally; those above 200 nm are rapidly sequestered by Kupffer cells and splenic macrophages (RES clearance). The optimal EPR window is approximately 10–200 nm. Surface PEGylation reduces RES uptake across all nanoparticle classes.
Nanoparticles and Cancer Immunotherapy
The most exciting frontier in nanomedicine is the intersection with cancer immunotherapy — exploiting nanoparticle pharmacokinetics to overcome the limitations of systemic immune checkpoint blockade and vaccination strategies.
Checkpoint inhibitor co-delivery: nanoparticles can co-encapsulate a cytotoxic agent (e.g., doxorubicin, paclitaxel) and an immunostimulatory payload (anti-PD-L1 antibody, STING agonist, or TLR agonist) in a single vehicle, creating a local immunostimulatory depot directly in the tumor. Intratumoral drug release induces immunogenic cell death (ICD) while simultaneously blocking inhibitory checkpoints on infiltrating T cells.
In situ vaccination: dying tumor cells release damage-associated molecular patterns (DAMPs) that, in combination with TLR agonist-loaded nanoparticles delivered intratumorally, activate local dendritic cells and generate systemic anti-tumor immunity — effectively turning the tumor itself into a vaccine site (Kwong et al., Nat Biotechnol 2013).
STING pathway activation: cyclic dinucleotide STING agonists (e.g., cGAMP, DMXAA analogs) encapsulated in LNPs activate the cGAS-STING innate immune axis in antigen-presenting cells within the tumor microenvironment, driving type I interferon production and CD8⁺ T-cell priming.
CAR-T cell support: systemic LNPs delivering IL-15, IL-21, or other cytokine-encoding mRNA can sustain CAR-T cell persistence and function in vivo without the toxicities associated with recombinant cytokine infusion.
Cell membrane-coated nanoparticles: coating nanoparticle cores with cancer cell-derived plasma membranes confers homotypic targeting — the nanoparticle is preferentially internalized by the tumor cells from which the membrane was sourced, exploiting natural cell-cell adhesion molecules for tumor specificity.
BioHippo Reagents for Nanoparticle and Immunotherapy Research
BioHippo does not manufacture nanoparticle formulations directly, but the catalog is well stocked with the assay reagents researchers need to evaluate nanocarrier efficacy — from target-expression profiling to cytokine readouts and immune checkpoint quantification.
Immune checkpoint ELISA kits for quantifying checkpoint protein release or expression in nanoparticle-treated co-cultures: the Mouse PD-L1/CD274 ELISA Kit (sandwich ELISA, 20–4,500 ng/L detection range, serum/plasma/cell culture supernatant) is validated for measuring PD-L1 shedding in tumor immunology models. CTLA-4 kits for both human and mouse cover the co-inhibitory checkpoint that PEGylated liposome + anti-CTLA4 combination studies routinely interrogate.
Cytokine ELISA kits: quantifying cytokine storm risk and immunostimulation potency is essential for LNP characterization. BioHippo carries an extensive panel including ELISA kits for IL-6, TNF-α, IFN-γ, IL-12, and chemokines (CXCL9/MIG, CCL18) relevant to nanoparticle-induced innate immune responses.
Cancer research antibodies: target validation before and after nanoparticle treatment — PD-L1, HER2, EpCAM, CD8α, FOXP3 — from the Cancer Antibodies collection (3,000+ validated antibodies). Explore the full Antibodies catalog for Western blot, IHC, and flow cytometry applications.
Browse the complete ELISA Kits collection (44,000+ kits) to identify assays that match your nanoparticle study design — from pharmacokinetic endpoints to immune profiling readouts.
Frequently Asked Questions
What are liposomes in cancer treatment?
Liposomes in cancer treatment are nanoscale spherical vesicles — typically 50–200 nm in diameter — bounded by a phospholipid bilayer that mimics cell membrane structure. They encapsulate chemotherapeutic agents or immunomodulatory payloads and deliver them preferentially to tumors by exploiting the EPR effect: tumor vasculature is abnormally leaky (fenestrated endothelium with pores up to 1,200 nm) and tumor lymphatic drainage is deficient, so circulating liposomes extravasate and accumulate in the tumor interstitium. PEGylated (stealth) liposomes evade immune clearance, extending their circulation half-life and increasing tumor drug exposure while reducing systemic toxicity. FDA-approved liposomal cancer drugs include Doxil (doxorubicin), Onivyde (irinotecan), and Marqibo (vincristine).
How do nanoparticles target cancer cells?
Nanoparticles target cancer cells via two complementary mechanisms. Passive targeting relies on the EPR effect — the leaky tumor vasculature and impaired lymphatic drainage that allow sub-200 nm particles to preferentially accumulate in solid tumors compared with normal tissues with intact vascular junctions. Active targeting adds a molecular recognition layer by conjugating tumor-specific ligands (monoclonal antibodies, nanobodies, peptides, aptamers, or small molecules such as folate or transferrin) to the nanoparticle surface. These ligands bind to receptors overexpressed on cancer cells — HER2, EpCAM, folate receptor α, EGFR — triggering receptor-mediated endocytosis and intracellular drug delivery. Active targeting increases cellular internalization but does not necessarily improve tumor biodistribution over passive EPR accumulation; the two approaches are complementary rather than mutually exclusive.
What is a lipid nanoparticle (LNP)?
A lipid nanoparticle (LNP) is a non-lamellar lipid assembly — structurally distinct from a liposome — comprising four components: an ionizable lipid, a helper phospholipid (commonly DSPC), a PEG-lipid, and cholesterol. The ionizable lipid is the key innovation: it carries a pKa of approximately 6.0–6.5, meaning it is largely uncharged at physiological pH (minimizing complement activation and toxicity during circulation) but becomes protonated in the acidic endosome (pH ~5.5), destabilizing the endosomal membrane and releasing nucleic acid cargo into the cytoplasm. LNPs were developed primarily for siRNA and mRNA delivery because their endosomal escape efficiency far exceeds that of classic liposomes. The COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) are LNP-formulated and proved the platform's clinical scalability. Cancer applications include mRNA-encoded tumor antigens, CRISPR components, and immunostimulatory RNA.
What is the difference between a liposome and a nanoparticle?
In the broadest sense, a liposome is a type of nanoparticle — all liposomes are nanoparticles, but not all nanoparticles are liposomes. The term nanoparticle covers any engineered particle in the 1–1,000 nm size range, including lipid, polymeric (PLGA, chitosan), metallic (gold, iron oxide), and silica-based systems. A liposome specifically is a lipid vesicle with a defined phospholipid bilayer enclosing an aqueous core — the bilayer is what distinguishes it from an LNP. An LNP lacks a defined aqueous core and bilayer; its interior has an inverted micellar structure. Practically, the choice between liposome and other nanoparticle types depends on cargo type (hydrophilic vs. hydrophobic small molecule vs. nucleic acid), required release kinetics, target cell biology, and manufacturing scale requirements.
What nanoparticle cancer drugs are FDA-approved?
Several nanoparticle-based cancer drugs have received FDA approval, spanning liposomal formulations and polymeric nanoparticles:
- Doxil (liposomal doxorubicin HCl) — FDA-approved 1995; Kaposi's sarcoma, ovarian cancer, multiple myeloma.
- DaunoXome (liposomal daunorubicin) — AIDS-related Kaposi's sarcoma.
- Marqibo (vincristine sulfate liposome injection) — adult ALL.
- Onivyde (liposomal irinotecan) — metastatic pancreatic cancer.
- Abraxane (nab-paclitaxel; albumin-bound paclitaxel nanoparticles) — metastatic breast cancer, NSCLC, pancreatic cancer.
- Vyxeos (liposomal daunorubicin + cytarabine) — newly diagnosed therapy-related AML.
This list continues to grow as nanocarrier platforms — particularly LNPs for nucleic acid delivery — advance through late-stage clinical trials.
References
- Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303(5665):1818–1822.
- Peer D, Karp JM, Hong S, et al. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2(12):751–760.
- Semple SC, Akinc A, Chen J, et al. Rational design of cationic lipids for siRNA delivery. Nat Biotechnol. 2010;28(2):172–176.
- Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer. 2017;18(1):20–37.
- Kwong B, Liu H, Irvine DJ. Induction of potent anti-tumor responses while eliminating systemic side effects via liposome-anchored combinatorial immunotherapy. Nat Biotechnol. 2013;31(8):790–797. doi:10.1038/nbt.2728
- Zong Y, Lin Y, Wei T, Cheng Q. Lipid Nanoparticle (LNP) enables mRNA delivery for cancer therapy. Adv Mater. 2023;35(51):e2303261.