RESUMO
Lysosome-targeting self-assembling prodrugs had emerged as an attractive approach to overcome the acquisition of resistance to chemotherapeutics by inhibiting lysosomal sequestration. Taking advantage of lysosomal acidification induced intracellular hydrolytic condensation, we developed a lysosomal-targeting self-condensation prodrug-nanoplatform (LTSPN) system for overcoming lysosome-mediated drug resistance. Briefly, the designed hydroxycamptothecine (HCPT)-silane conjugates self-assembled into silane-based nanoparticles, which were taken up into lysosomes by tumor cells. Subsequently, the integrity of the lysosomal membrane was destructed because of the acid-triggered release of alcohol, wherein the nanoparticles self-condensed into silicon particles outside the lysosome through intracellular hydrolytic condensation. Significantly, the LTSPN system reduced the half-maximal inhibitory concentration (IC50) of HCPT by approximately 4 times. Furthermore, the LTSPN system realized improved control of large established tumors and reduced regrowth of residual tumors in several drug-resistant tumor models. Our findings suggested that target destructing the integrity of the lysosomal membrane may improve the therapeutic effects of chemotherapeutics, providing a potent treatment strategy for malignancies.
Assuntos
Nanopartículas , Neoplasias , Pró-Fármacos , Linhagem Celular Tumoral , Resistência a Medicamentos , Humanos , Lisossomos/patologia , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Silanos/farmacologia , Silanos/uso terapêuticoRESUMO
Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.
Assuntos
Berberina , Colite Ulcerativa , Colite , Medicamentos de Ervas Chinesas , Nanopartículas , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Ácido Ursodesoxicólico/efeitos adversos , Berberina/farmacologia , Interleucina-6 , Fator de Necrose Tumoral alfa/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Colo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Colite/induzido quimicamenteRESUMO
Proteolysis targeting chimera (PROTAC) is an emerging pharmacological modality with innovated post-translational protein degradation capabilities. However, off-target induced unintended tissue effects and intrinsic "hook effect" hinder PROTAC biotechnology to be maturely developed. Herein, an intracellular fabricated nano proteolysis targeting chimeras (Nano-PROTACs) modality with a center-spoke degradation network for achieving efficient dose-dependent protein degradation in tumor is reported. The PROTAC precursors are triggered by higher GSH concentrations inside tumor cells, which subsequently in situ self-assemble into Nano-PROTACs through intermolecular hydrogen bond interactions. The fibrous Nano-PROTACs can form effective polynary complexes and E3 ligases degradation network with multi-binding sites, achieving dose-dependent protein degradation with "anti-hook effect". The generality and efficacy of Nano-PROTACs are validated by degrading variable protein of interest (POI) such as epidermal growth factor receptor (EGFR) and androgen receptor (AR) in a wide-range dose-dependent manner with a 95 % degradation rate and long-lasting potency up to 72â h in vitro. Significantly, Nano-PROTACs achieve in vivo dose-dependent protein degradation up to 79 % and tumor growth inhibition in A549 and LNCap xenograft mice models, respectively. Taking advantages of in situ self-assembly strategy, the Nano-PROTACs provide a generalizable platform to promote precise clinical translational application of PROTAC.
Assuntos
Neoplasias , Ubiquitina-Proteína Ligases , Humanos , Animais , Camundongos , Proteólise , Ubiquitina-Proteína Ligases/metabolismo , Proteínas/metabolismo , Sítios de LigaçãoRESUMO
Intravesical administration of first-line drugs has shown failure in the treatment of bladder cancer owing to the poor tumor retention time of chemotherapeutics. Herein, we report an intracellular hydrolytic condensation (IHC) system to construct long-term retentive nano-drug depots in situ, wherein sustained drug release results in highly efficient suppression of bladder cancer. Briefly, the designed doxorubicin (Dox)-silane conjugates self-assemble into silane-based prodrug nanoparticles, which condense into silicon particle-based nano-drug depots inside tumor cells. Significantly, we demonstrate that the IHC system possesses highly potent antitumor efficacy, which leads to the regression and eradication of large established tumors and simultaneously extends the overall survival of air pouch bladder cancer mice compared with that of mice treated with Dox. The concept of intracellular hydrolytic condensation can be extended via conjugating other chemotherapeutic drugs, which may facilitate rational design of novel nanomedicines for augmentation of chemotherapy.
Assuntos
Antineoplásicos , Nanopartículas , Neoplasias da Bexiga Urinária , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Masculino , Camundongos , Nanopartículas/uso terapêutico , Silanos , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
As a continuation of our research on developing potent and potentially safe androgen receptor (AR) degrader, a series of novel proteolysis targeting chimeras (PROTACs) containing the phthalimide degrons with different linker were designed, synthesized and evaluated for their AR degradation activity against LNCaP (AR+) cell line. Most of the synthesized compounds displayed moderate to satisfactory AR binding affinity and might lead to antagonist activity against AR. Among them, compound A16 exhibited the best AR binding affinity (85%) and degradation activity against AR. Due to the strong fluorescence properties of pomalidomide derivatives, B10 was found to be effectively internalized and visualized in LNCaP (AR + ) cells than PC-3 (AR-) cells. Moreover, the molecular docking of A16 with AR and the active site of DDB1-CRBN E3 ubiquitin ligase complex provides guidance to design new PROTAC degrons targeting AR for prostate cancer therapy. These results represent a step toward the development of novel and improved AR PROTACs.
Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Neoplasias da Próstata/tratamento farmacológico , Proteólise/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Modelos Moleculares , Estrutura Molecular , Neoplasias da Próstata/metabolismo , Relação Estrutura-AtividadeRESUMO
The Src homology-2 domain containing-protein tyrosine phosphatase-2 (SHP2) is a convergent node for oncogenic cell-signaling cascades including the PD-L1/PD-1 pathway. As an oncoprotein as well as a potential immunomodulator, SHP2 has now emerged as an attractive target for novel anti-cancer agents. Although significant progress has been made in identifying chemotypes of SHP2 inhibitors, these specific compounds might not be clinically useful to inhibit frequently encountered mutated SHP2 variants. Consequently, it is highly desirable to develop chemically different SHP2 inhibitors sensitive to SHP2 mutants. This work developed a new type of SHP2 inhibitors with 2,5-diaryl-1,3,4-oxadiazole scaffold. The representative compound 6l exhibited SHP2 inhibitory activity with IC50 of 2.73 ± 0.20 µM, showed about 1.56-fold, 5.26-fold, and 7.36-fold selectivity for SHP2 over SHP1, PTP1B and TCPTP respectively. Further investigations confirmed that 6l behaved as mixed-type inhibitor sensitive to leukemia cell TF-1 and inhibited SHP2 mediated cell signaling and proliferation. Molecular dynamics simulation provided more detailed information on the binding modes of compounds and SHP2 protein. These preliminary results could provide a possible opportunity for the development of novel SHP2 inhibitors sensitive to SHP2 mutants with optimal potency and improved pharmacological properties.
Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Oxidiazóis/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Simulação de Dinâmica Molecular , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Relação Estrutura-AtividadeRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most widespread type of non-Hodgkin lymphoma (NHL). As the most aggressive form of the DLBCL, the activated B-cell-like (ABC) subtype is often resistant to standard chemotherapies. Bruton's tyrosine kinase (BTK) inhibitor ibrutinib provides a potential therapeutic approach for the DLBCL but fails to improve the outcome in the phase III trial. In the current study, we investigated the molecular mechanisms underlying ibrutinib resistance and explored new combination therapy with ibrutinib. We generated an ibrutinib-resistant ABC-DLBCL cell line (OCI-ly10-IR) through continuous exposure to ibrutinib. Transcriptome analysis of the parental and ibrutinib-resistant cell lines revealed that the ibrutinib-resistant cells had significantly lower expression of the unfolded protein response (UPR) marker genes. Overexpression of one UPR branch-XBP1s greatly potentiated ibrutinib-induced apoptosis in both sensitive and resistant cells. The UPR inhibitor tauroursodeoxycholic acid (TUDCA) partially reduced the apoptotic rate induced by the ibrutinib in sensitive cells. The UPR activator 2-deoxy-D-glucose (2-DG) in combination with the ibrutinib triggered even greater cell growth inhibition, apoptosis, and stronger calcium (Ca2+) flux inhibition than either of the agents alone. A combination treatment of ibrutinib (15 mg·kg-1·d-1, po.) and 2-DG (500 mg/kg, po, b.i.d.) synergistically retarded tumor growth in NOD/SCID mice bearing OCI-ly10-IR xenograft. In addition, ibrutinib induced the UPR in the sensitive cell lines but not in the resistant cell lines of the DLBCL. There was also a combined synergistic effect in the primary resistant DLBCL cell lines. Overall, our results suggest that targeting the UPR could be a potential combination strategy to overcome ibrutinib resistance in the DLBCL.
Assuntos
Adenina/análogos & derivados , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Piperidinas/uso terapêutico , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Adenina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desoxiglucose/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/fisiologia , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/fisiopatologia , Camundongos Endogâmicos NOD , Camundongos SCID , Resposta a Proteínas não Dobradas/fisiologia , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, the wide application of GPX4 inhibitors in tumor therapy is hampered due to poor tumor delivery efficacy and the nonspecific activation of ferroptosis. Taking advantage of in vivo self-assembly, we develop a peptide-ferriporphyrin conjugate with tumor microenvironment specific activation to improve tumor penetration, endocytosis and GPX4 inhibition, ultimately enhancing its anticancer activity via ferroptosis. Briefly, a GPX4 inhibitory peptide is conjugated with an assembled peptide linker decorated with a pH-sensitive moiety and ferriporphyrin to produce the peptide-ferriporphyrin conjugate (Gi-F-CAA). Under the acidic microenvironment of the tumor, the Gi-F-CAA self-assembles into large nanoparticles (Gi-F) due to enhanced hydrophobic interaction after hydrolysis of CAA, improving tumor endocytosis efficiency. Importantly, Gi-F exhibits substantial inhibition of GPX4 activity by assembly enhanced binding (AEB) effect, augmenting the oxidative stress of ferriporphyrin-based Fenton reaction, ultimately enabling antitumor properties in multiple tumor models. Our findings suggest that this peptide-ferriporphyrin conjugate design with AEB effect can improve the therapeutic effect via induction of ferroptosis, providing an alternative strategy for overcoming chemoresistance.
Assuntos
Ferroptose , Neoplasias , Humanos , Endocitose , Hemina , Hidrólise , Peptídeos/farmacologia , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
Anti-PD-L1 monoclonal antibody has achieved substantial success in tumor immunotherapy by T-cells activation. However, the excessive accumulation of extracellular matrix components induced by unsatisfactory T-cells infiltration and poor tumor penetration of antibodies make it challenging to realize efficient tumor immunotherapy. Herein, a peptide-based bispecific nanoblocker (BNB) strategy is reported for in situ construction of CXCR4/PD-L1 targeted nanoclusters on the surface of tumor cells that are capable of boosting T-cells infiltration through CXCR4 blockage and enhancing T-cells activation by PD-L1 occupancy, ultimately realizing high-performance tumor immunotherapy. Briefly, the BNB strategy selectively recognizes and bonds CXCR4/PD-L1 with deep tumor penetration, which rapidly self-assembles into nanoclusters on the surface of tumor cells. Compared to the traditional bispecific antibody, BNB exhibits an intriguing metabolic behavior, that is, the elimination half-life (t1/2 ) of BNB in the tumor is 69.3 h which is ≈50 times longer than that in the plasma (1.4 h). The higher tumor accumulation and rapid systemic clearance overcome potential systemic side effects. Moreover, the solid tumor stress generated by excessive extracellular matrix components is substantially reduced to 44%, which promotes T-cells infiltration and activation for immunotherapy efficacy. Finally, these findings substantially strengthen and extend clinical applications of PD-1/PD-L1 immunotherapy.
Assuntos
Anticorpos Biespecíficos , Neoplasias , Humanos , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Neoplasias/terapia , Anticorpos Biespecíficos/uso terapêutico , Linfócitos T/metabolismo , ImunoterapiaRESUMO
Up to 75% of bladder cancer patients suffer from recurrence due to postoperative tumor implantation. However, clinically used Bacillus Calmette-Guerin (BCG) treatment failed to inhibit the recurrence. Here, we report a bispecific glycopeptide (bsGP) that simultaneously targets CD206 on tumor-associated macrophages (TAMs) and CXCR4 on tumor cells. bsGP repolarizes protumoral M2-like TAMs to antitumor M1-like that mediated cytotoxicity and T cell recruitment. Meanwhile, bsGP is cleaved by the MMP-2 enzyme to form nanostructure for the long-term inhibition of CXCR4 downstream signaling, resulting in reduced tumor metastasis and promoted T cell infiltration. In orthotopic bladder tumor models, bsGP reduced the postoperative recurrence rate to 22%. In parallel, the recurrence rates of 89 and 78% were treated by doxycycline and BCG used in clinic, respectively. Mechanistic studies reveal that bsGP reduces the matrix microenvironment barrier, increasing the spatially redirected CD8+ T cells to tumor cells. We envision that bis-targeting CD206 and CXCR4 may pave the way to inhibit tumor metastasis and recurrence.
Assuntos
Microambiente Tumoral , Neoplasias da Bexiga Urinária , Humanos , Vacina BCG , Linfócitos T CD8-Positivos , Recidiva Local de Neoplasia , GlicopeptídeosRESUMO
Jiyuan Oridonin A (JOA) is a naturally occurring ent-kaurane diterpenoid that exhibits significant potential in the field of anti-tumor drug development. However, its detailed anti-cancer mechanism of action has not been fully understood. In order to investigate its anticancer mode of action, two series of novel fluorescent derivatives of JOA conjugated with naphthalimide dyes were synthesized, and their antitumor activity against five selected cancer cell lines (MGC-803, SW1990, PC-3, TE-1 and HGC-27) was evaluated. Compared with JOA, the anti-tumor activity of the vast majority of compounds were improved. Among them, B12 exhibited promising anti-proliferative activity against HGC-27 cells with IC50 value of 0.39 ± 0.09 µM. Fluorescence imaging studies demonstrated that probe B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. Preliminary biological mechanism studies indicated that B12 was able to inhibit cell cloning and migration. Further studies suggested that B12-induced apoptosis was related to the mitochondrial pathway. Overall, our results provide new approaches to explore the molecular mechanism of the natural product JOA, which would contribute to its further development as an antitumor agent.
Assuntos
Antineoplásicos/síntese química , Diterpenos do Tipo Caurano/química , Corantes Fluorescentes/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diterpenos do Tipo Caurano/síntese química , Diterpenos do Tipo Caurano/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Relação Estrutura-AtividadeRESUMO
Intraoperative fluorescence-based tumor imaging plays a crucial role in performing the oncological safe tumor resection with the advantage of differentiating tumor from normal tissues. However, the application of these fluorescence contrast agents in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) was dramatically hammered as a result of lacking active targeting and poor retention time in tumor, which limited the Signal to Noise Ratio (SNR) and narrowed the imaging window for complicated surgery. Herein, we reported an activated excretion-retarded tumor imaging (AERTI) strategy, which could be in situ activated with MMP-2 and self-assembled on the surface of tumor cells, thereby resulting in a promoted excretion-retarded effect with an extended tumor retention time and enhanced SNR. Briefly, the AERTI strategy could selectively recognize the Integrin αvß3. Afterwards, the AERTI strategy would be activated and in situ assembled into nanofibrillar structure after specifically cleaved by MMP-2 upregulated in a variety of human tumors. We demonstrated that the AERTI strategy was successfully accumulated at the tumor sites in the 786-O and HepG2 xenograft models. More importantly, the modified modular design strategy obviously enhanced the SNR of AERTI strategy in the imaging of orthotopic RCC and HCC. Taken together, the results presented here undoubtedly confirmed the design and advantage of this AERTI strategy for the imaging of tumors in metabolic organs.
RESUMO
Tumor cells intensively engage in metabolic reprogramming for enhancing the availability of glycolytic metabolites and support cell proliferation. As the most important rate-limiting enzyme in aerobic glycolysis, activating the pyruvate kinase muscle isoform 2 (PKM2) from dimers to tetramers has become a key tumor chemotherapy method to control glucose metabolism. Herein, we developed a glycopeptide-based PKM2 nano-activator, which could induce the tetramerization of PKM2 based on serine bonding to Domain C of PKM2. The bound and trapped PKM2 tetramers significantly hindered glycolytic intermediates, prevented the nucleus translocation of dimeric PKM2, and ultimately inhibited the proliferation, chemoresistance and metastasis of tumor. The glycopeptide assembled into nanoparticles under aqueous conditions and in the circulation, which in situ transformed into PKM2 nano-activator with nanofibrillar structure after specifically activated by O-GlcNAcase recognition upregulated in a wide range of human tumors. Moreover, the glycopeptide-based PKM2 nano-activator successfully accumulated at the tumor sites and boosted the chemo-drug sensitivity against prostate and breast cancers. Attributed to these intriguing results, the newly developed glycopeptide-based PKM2 nano-activator can be envisioned a promising candidate for the treatment of tumors by switching catabolic pathways.
Assuntos
Neoplasias da Mama , Piruvato Quinase , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Glicólise , Glicopeptídeos/metabolismo , Humanos , Masculino , Músculos/metabolismo , Isoformas de Proteínas/metabolismo , Piruvato Quinase/metabolismoRESUMO
Peptide drug conjugate (PDC) has emerged as one of the new generations of targeted therapeutics for cancer, which owns the advantages of improved drug targetability and reduced adverse effects compared with traditional chemotherapy. However, the poor permeability of PDC drugs regarding tumor cells is an urgent problem to be solved. Herein, we design a PDC drug molecule, which is composed of three modules: targeting motif (RGD target), assembly motif (GNNNQNY) and cytotoxic payload (CPT molecule). This PDC in situ forms nanoclusters upon binding cellular receptor, resulting in improved PDC cell-entry efficiency and treatment efficacy. In addition, the PDC shows increased therapeutic efficacy and raises the maximum tolerance dose of the drug in breast and bladder xenografted mice models. This strategy leverages the assembly principle to promote penetration of peptide molecules into cells and increase intracellular drug bioavailability, which is of great significance for the development of PDC drugs in the future.
Assuntos
Antineoplásicos , Preparações Farmacêuticas , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Camundongos , PeptídeosRESUMO
A series of 2-ethoxycarbonylthieno[2,3-b]quinolines were synthesized in the bio-derived "green" solvent γ-valerolactone (GVL) and evaluated for their inhibitory activities against PTP1B, the representative compound 6a displayed an IC50 value of 8.04 ± 0.71 µM with 4.34-fold preference over TCPTP. These results provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.
RESUMO
OBJECTIVE: To study the alterations and relationship of surfactant protein (SP)-A, SP-D and KL-6 in serum and bronchoalveolar lavage fluids (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP). METHOD: Self-control method was used for the study on SP-A, SP-D and KL-6 in serum, infected and non-infected BALFs in 32 MMP children with only one side of MPP. RESULT: The contents of SP-A, SP-D and KL-6 in infected BALF were [mg/L;M (IQR) ]: 243 (90-468) , 187 (43-333) , 148 (47-426) ;104 (37-257) , 56 (25-131) , 35 (12-147) in non-infected BALF; 35 (25-69) , 33 (9-149) and 24 (15-62) in serum. The correlation coefficient of KL-6 between serum and infected BALF were -0.534 and -0.378 (P < 0.05). CONCLUSION: There were significant correlation between the alterations of SP-A, SP-D and KL-6 in serum and lung infection in children with CAP. KL-6 in serum may be more sensitive than SP-A and SP-D.