# Nanomedicine-based lactate metabolism and lactylation regulation for exploring new therapeutic strategies in cancer **Authors:** Shuzhe Cai, Siqi Li, Jingjing Liu PMC · DOI: 10.1016/j.mtbio.2026.102893 · Materials Today Bio · 2026-02-05 ## TL;DR This paper reviews how nanomedicine can target lactate metabolism and lactylation to develop new cancer therapies. ## Contribution The paper introduces multifunctional nanoplatforms that simultaneously regulate lactate and lactylation for cancer treatment. ## Key findings - Nanomedicine can modulate lactate production, transport, and clearance in tumors. - Lactylation regulation via lactyl-CoA and enzymes offers new therapeutic targets. - Combining metabolic and epigenetic interventions could enhance cancer treatment. ## Abstract Lactate, a key metabolite of glycolysis in tumor cells, plays a dual role in cancer progression. On one hand, it contributes to the formation of an acidic tumor microenvironment that fosters tumorigenesis and malignancy. On the other, it promotes tumor progression through protein lactylation, a recently identified post-translational modification. Consequently, targeting lactate metabolism and lactylation represents a critical therapeutic method in oncology. Advances in nanomedicine have opened new possibilities for precise modulation of lactate metabolism. Nanomedicine-based strategies enable the regulation of lactate production, transport, and clearance, thereby offering effective tools for tumor suppression. Additionally, the lactate induced lactylation orchestrated by lactyl-CoA, lactyltransferases, and delactylases offer more refined targets for investigating approaches to inhibit tumor progression. In this review, we comprehensively summarize recent developments in nanomedicine-based strategies for lactate metabolism modulation and the mechanism of lactylation regulation. We suppose the design of multifunctional nanoplatforms capable of simultaneously regulating lactate levels and lactylation could integrate metabolic and epigenetic interventions to disrupt lactate-driven tumor support mechanisms precisely and effectively for advancing cancer treatment paradigms. Image 1 ## Linked entities - **Diseases:** cancer (MONDO:0004992) ## Full-text entities - **Genes:** Ctla4 (cytotoxic T-lymphocyte-associated protein 4) [NCBI Gene 12477] {aka Cd152, Ctla-4, Ly-56}, ACSS2 (acyl-CoA synthetase short chain family member 2) [NCBI Gene 55902] {aka ACAS2, ACECS, ACS, ACSA, AceCS1, dJ1161H23.1}, AARS1 (alanyl-tRNA synthetase 1) [NCBI Gene 16] {aka AARS, CMT2N, DEE29, EIEE29, HDLS2, TTD8}, SLC16A3 (solute carrier family 16 member 3) [NCBI Gene 9123] {aka MCT 3, MCT 4, MCT-3, MCT-4, MCT3, MCT4}, Ldhb (lactate dehydrogenase B) [NCBI Gene 16832] {aka H-Ldh, LDH-B, LDH-H, Ldh-2, Ldh2}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Hk2 (hexokinase 2) [NCBI Gene 15277] {aka HKII}, CAT (catalase) [NCBI Gene 847], Cd47 (CD47 antigen (Rh-related antigen, integrin-associated signal transducer)) [NCBI Gene 16423] {aka 9130415E20Rik, B430305P08Rik, IAP, Itgp}, Mcat (malonyl CoA:ACP acyltransferase (mitochondrial)) [NCBI Gene 223722], XRCC1 (X-ray repair cross complementing 1) [NCBI Gene 7515] {aka RCC, SCAR26}, Acsl1 (acyl-CoA synthetase long-chain family member 1) [NCBI Gene 14081] {aka Acas, Acas1, Acs, FACS, Facl2, LACS 1}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, NBN (nibrin) [NCBI Gene 4683] {aka AT-V1, AT-V2, ATV, NBS, NBS1, P95}, Aars2 (alanyl-tRNA synthetase 2, mitochondrial) [NCBI Gene 224805] {aka Aarsl, AlaRS, Gm89}, Sirt3 (sirtuin 3) [NCBI Gene 64384] {aka 2310003L23Rik, Sir2l3}, SLC16A1 (solute carrier family 16 member 1) [NCBI Gene 6566] {aka HHF7, MCT, MCT1, MCT1D}, LOX (lysyl oxidase) [NCBI Gene 4015] {aka AAT10}, HK2 (hexokinase 2) [NCBI Gene 3099] {aka HKII, HXK2}, RAD50 (RAD50 double strand break repair protein) [NCBI Gene 10111] {aka NBSLD, RAD502, hRad50}, Cdkn1a (cyclin dependent kinase inhibitor 1A) [NCBI Gene 12575] {aka CAP20, CDKI, CIP1, Cdkn1, P21, SDI1}, KAT5 (lysine acetyltransferase 5) [NCBI Gene 10524] {aka ESA1, HTATIP, HTATIP1, NEDFASB, PLIP, TIP}, Bbc3 (BCL2 binding component 3) [NCBI Gene 170770] {aka PUMA, PUMA/JFY1}, PKLR (pyruvate kinase L/R) [NCBI Gene 5313] {aka CNSHA2, PK1, PKL, PKRL, RPK}, LUC7L2 (LUC7 like 2, pre-mRNA splicing factor) [NCBI Gene 51631] {aka CGI-59, CGI-74, LUC7B2}, Yap1 (yes-associated protein 1) [NCBI Gene 22601] {aka Yap, Yap65, Yki, Yorkie}, Sirt2 (sirtuin 2) [NCBI Gene 64383] {aka 5730427M03Rik, SIR2L2, Sir2l}, Apoe (apolipoprotein E) [NCBI Gene 11816] {aka Apo-E}, Aldh1a3 (aldehyde dehydrogenase family 1, subfamily A3) [NCBI Gene 56847] {aka ALDH6, RALDH3, V1}, Cgas (cyclic GMP-AMP synthase) [NCBI Gene 214763] {aka E330016A19Rik, Mb21d1}, Ldhc (lactate dehydrogenase C) [NCBI Gene 16833] {aka LDH-C4, Ldh-3, Ldh-x, Ldh3, Ldhc4}, Xrcc1 (X-ray repair complementing 1) [NCBI Gene 22594] {aka Xrcc-1}, PKM (pyruvate kinase M1/2) [NCBI Gene 5315] {aka CTHBP, HEL-S-30, OIP3, PK3, PKM2, TCB}, Cnpy3 (canopy FGF signaling regulator 3) [NCBI Gene 72029] {aka 1600025D17Rik, 2410050O22Rik, CAG4A, ERDA5, PRAT4A, Tnrc5}, Ldha (lactate dehydrogenase A) [NCBI Gene 16828] {aka Ldh1, Ldhm, l7R2}, Sptbn4 (spectrin beta, non-erythrocytic 4) [NCBI Gene 80297] {aka 1700022P15Rik, 5830426A08Rik, ROSA62, SpbIV, Spnb4, dyn}, Ttk (Ttk protein kinase) [NCBI Gene 22137] {aka Esk1, Mps1, PYT, esk}, Mettl16 (methyltransferase 16, N6-methyladenosine) [NCBI Gene 67493] {aka 2610100D03Rik, 2810013M15Rik, A830095F14Rik, Mett10d}, LDHA (lactate dehydrogenase A) [NCBI Gene 3939] {aka GSD11, HEL-S-133P, LDHM, PIG19}, Ccne2 (cyclin E2) [NCBI Gene 12448], Hectd2 (HECT domain E3 ubiquitin protein ligase 2) [NCBI Gene 226098] {aka 4921524L07, A630025O09Rik}, Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Nmnat1 (nicotinamide nucleotide adenylyltransferase 1) [NCBI Gene 66454] {aka 2610529L11Rik, 5730441G13Rik, D4Cole1e, nmnat}, Ep300 (E1A binding protein p300) [NCBI Gene 328572] {aka A430090G16, A730011L11, KAT3B, p300, p300 HAT}, Slc16a3 (solute carrier family 16 (monocarboxylic acid transporters), member 3) [NCBI Gene 80879] {aka Mct3, Mct4}, Tead1 (TEA domain family member 1) [NCBI Gene 21676] {aka 2610024B07Rik, B230114H05Rik, Gtrgeo5, TEAD-1, TEF-1, Tcf13}, SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825] {aka PD1, PPP1R145, tamo}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], Oga (O-GlcNAcase) [NCBI Gene 76055] {aka Hy5, Mgea5, Ncoat}, Fdx1 (ferredoxin 1) [NCBI Gene 14148], Rtn4r (reticulon 4 receptor) [NCBI Gene 65079] {aka NOGOR, NgR, NgR1}, MLH1 (mutL homolog 1) [NCBI Gene 4292] {aka COCA2, FCC2, HNPCC, HNPCC2, LYNCH2, MLH-1}, Pcsk9 (proprotein convertase subtilisin/kexin type 9) [NCBI Gene 100102] {aka FH3, HCHOLA3, Narc1, PC9}, Sirpa (signal-regulatory protein alpha) [NCBI Gene 19261] {aka Bit, CD172a, Idd13.2, P84, Ptpns1, SHP-1}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, Sirt1 (sirtuin 1) [NCBI Gene 93759] {aka SIR2L1, Sir2, Sir2a, Sir2alpha}, Kat2a (K(lysine) acetyltransferase 2A) [NCBI Gene 14534] {aka 1110051E14Rik, Gcn5, Gcn5l2, mmGCN5}, Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1} - **Diseases:** acid toxicity (MESH:D064420), cardiovascular disease (MESH:D002318), ICD (MESH:D003643), CRC (MESH:D015179), metastasis (MESH:D009362), GBM (MESH:D005909), RCC (MESH:D002292), sepsis (MESH:D018805), chronic (MESH:D002908), solid (MESH:D018250), hepatocellular carcinoma (MESH:D006528), breast cancer (MESH:D001943), calcium (MESH:D002128), lung cancer (MESH:D008175), cancers (MESH:D009369), pancreatic cancer (MESH:D010190), PDAC (MESH:D021441), inflammation (MESH:D007249), prostate cancer (MESH:D011471), calcium overload (MESH:D019190), fibrosis (MESH:D005355), melanoma (MESH:D008545), glioma (MESH:D005910), Hypoxia (MESH:D000860), metabolic alkalosis (MESH:D000471), tumorigenesis (MESH:D063646), TAM (MESH:D020914), gastric cancer (MESH:D013274), hypoxic (MESH:D002534) - **Chemicals:** ammonium bicarbonate (MESH:C027043), Serine (MESH:D012694), CoA (MESH:D003065), Se (MESH:D012643), HCO3- (MESH:D001639), succinyl-CoA (MESH:C012046), GlcNAc (MESH:D000117), L-Arg (MESH:D001120), GSK (MESH:C000612070), AZD3965 (MESH:C000592351), CHC (MESH:C007175), TMZ (MESH:D000077204), DOX (MESH:D004317), Na+ (MESH:D012964), disodium hydrogen phosphate (MESH:C018279), PAH (MESH:C063994), disulfide (MESH:D004220), Co3+ (-), IR780 (MESH:C548458), H2O2 (MESH:D006861), porphyrin (MESH:D011166), NaHCO3 (MESH:D017693), CDDP (MESH:D002945), MPB (MESH:C012415), sulfur (MESH:D013455), zirconium- (MESH:D015040), glucose (MESH:D005947), APS (MESH:C031276), calcium (MESH:D002118), ROS (MESH:D017382), methacrylate (MESH:D008689), lysine (MESH:D008239), PLGA (MESH:D000077182), dopamine (MESH:D004298), NAD+ (MESH:D009243), PBS (MESH:D007854), PLDs (MESH:C041277), lipid (MESH:D008055), OH (MESH:C031356), fluvastatin (MESH:D000077340), lenvatinib (MESH:C531958), olaparib (MESH:C531550), agarose (MESH:D012685), CS (MESH:D002586), ATP (MESH:D000255), polyphenols (MESH:D059808), Stiripentol (MESH:C021092), GSH (MESH:D005978), Co2+ (MESH:D002245), N, N, N',N'-Tetramethyl ethylenediamine (MESH:C005798), beta-alanine (MESH:D015091), glutamine (MESH:D005973), FMN (MESH:D005486), Co (MESH:D003035), 2-DG (MESH:D003847), TPZ (MESH:D000077704), HPP (MESH:C085216), lonidamine (MESH:C016371), alanine (MESH:D000409), entinostat (MESH:C118739) - **Species:** Homo sapiens (human, species) [taxon 9606], Gluconobacter oxydans (species) [taxon 442], Staphylococcus aureus (species) [taxon 1280], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Shewanella oneidensis (species) [taxon 70863], Mus musculus (house mouse, species) [taxon 10090], Escherichia coli (E. coli, species) [taxon 562], Anaerobutyricum hallii (species) [taxon 39488], Veillonella atypica (species) [taxon 39777] - **Cell lines:** U87 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0022), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), NCI-H1395 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_1467), BEAS-2B — Homo sapiens (Human), Transformed cell line (CVCL_0168), GL261 — Mus musculus (Mouse), Mouse glioblastoma, Cancer cell line (CVCL_Y003) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12914674/full.md ## Figures 16 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12914674/full.md ## References 121 references — full list in the complete paper: https://tomesphere.com/paper/PMC12914674/full.md --- Source: https://tomesphere.com/paper/PMC12914674