Research Progress of Osimertinib Supported by Nanodrug Delivery System Against Non-small Cell Lung Cancer
-
摘要:
奥希替尼是不可逆的第三代表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)，用于治疗经典EGFR突变和T790M耐药突变的非小细胞肺癌(NSCLC)。然而，与其他EGFR-TKIs一样，奥希替尼不可避免地存在获得性耐药、水溶性差、肿瘤累积率低等问题，限制了其治疗效果。纳米递药系统可增加药物的溶解度和稳定性，延长药物血液循环时间，提高细胞摄取率，增加在肿瘤组织中的聚集改善药物耐药问题，已成为解决传统靶向药物弊端的有效手段。本文综述了第三代EGFR-TKI奥希替尼的作用机制，重点阐述了奥希替尼纳米递药系统抗NSCLC的研究进展，并对该领域面临的挑战和未来发展方向进行了展望。
Abstract:Osimertinib is an irreversible third representative epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of non-small cell lung cancer (NSCLC) with T790M resistance and classical EGFR mutations. However, the therapeutic effectiveness of osimertinib is limited by acquired drug-resistance, poor water solubility and low tumor accumulation rates. Nanodrug delivery systems can increase the solubility and stability of drugs, prolong the blood circulation time of drugs, improve the uptake rate of cells, promote drug accumulation in tumor tissues, and improve drug resistance. Thus, they are effective in overcoming the limitations of traditional targeted drugs. In this study, we reviewed the mechanism of action of the third-generation EGFR-TKI osimertinib, focused on research advances in osimertinib nanodrug delivery systems against NSCLC, and explored the challenges and future development direction in this field.
-
Key words:
- NSCLC /
- Osimertinib /
- Nanodrug delivery system
-
0 引言
子宫内膜癌位于我国妇女生殖道恶性肿瘤的第二位，仅次于宫颈癌，占全部女性生殖系统恶性肿瘤的20%~30%[1]。尽管子宫内膜癌的诊断治疗有了迅速发展，但仍有5%~15%的早期子宫内膜癌不仅复发且有较高的死亡率[2]。因此研究Ⅰ~Ⅱ期子宫内膜癌复发相关危险因素，从而有效干预是目前关注的重点。本研究就此进行具体分析，现报告如下。
1 资料与方法
1.1 一般资料
采用回顾性研究方法收集南京鼓楼医院2010年1月~2017年12月期间收治的子宫内膜癌手术患者747例，随访606例，失访141例，最后归纳516例初始诊断为Ⅰ~Ⅱ期子宫内膜癌的患者作为研究对象，住院患者均有不同程度的阴道流血、分泌物增多、腹痛等。按照国际妇产科联盟FIGO 2009规定的“子宫内膜癌手术-病理分期”标准，确定其病理类型及术后分期。患者年龄24~83岁，平均年龄（57.07±10.63）岁。排除标准:术前放化疗、心肺肝肾功能不全、急性感染、凝血异常、自身免疫性疾病、子宫内膜癌为第二原发癌等患者。
1.2 方法
回顾全部患者的基本信息及有关病史详细记载，统计有关生化及影像学检查。全部患者行全面分期手术，部分患者根据淋巴浸润、病理分级等术后辅助放化疗或激素治疗。首次手术术中标本均采用免疫组织化学法（IHC）检测雌激素受体（ER）和孕激素受体（PR），根据染色程度采用积分综合测量分类。门诊及电话随访1~8年。按照复发与否分为复发组和未复发组。复发是指在阴道残端、腹股沟区、肺部、骨、盆腔等出现肿瘤，经生化肿瘤相关指标、妇科B型超声、盆腔（增强）CT或MRI、PET-CT、病理学等检查确诊。
1.3 统计学方法
用SPSS22.0软件包进行数据处理，（x±s）表示正态分布且方差齐的计量资料，比较用t检验。计数资料用百分数表示，组间比较用χ2检验。非参数资料采用秩和检验，Logistic多因素回归进行危险因素分析。P < 0.05为差异有统计学意义。
2 结果
2.1 复发情况
在516例Ⅰ~Ⅱ期子宫内膜癌患者中，46例复发，复发率为8.91%，平均复发时间间隔为（19.47 ±13.79）月；其中盆腔复发16例。转移30例：8例阴道下段转移、8例肺转移、3例腹股沟淋巴结转移、6例骨转移、其余5例出现其他部位转移。46例复发患者中30例入院再次治疗后复发病灶消失，其余16例死亡（3例死于其他疾病）。
2.2 影响Ⅰ~Ⅱ期子宫内膜癌复发的单因素分析
对影响Ⅰ~Ⅱ期子宫内膜癌复发的单因素分析显示，高龄、低体重、高血压、手术病理分期、病理类型、ER及PR低表达与Ⅰ~Ⅱ期子宫内膜癌复发存在一定相关性，两组间比较差异有统计学意义（P < 0.05）；糖尿病、脉管转移、病理分化程度、淋巴结切除、腹水细胞学检查比较差异无统计学意义（P > 0.05），见表 1。
表 1 影响Ⅰ~Ⅱ期子宫内膜癌复发的单因素关系分析(x±s)Table 1 Univariate analysis of influence factors for recurrence of stage Ⅰ-Ⅱ endometrial cancer (x±s)
2.3 影响Ⅰ~Ⅱ期子宫内膜癌复发的独立危险因素分析
对单因素分析中P < 0.20的因素进行多因素Cox比例风险回归模型进行分析，结果表明：年龄、体重、血压是Ⅰ~Ⅱ期子宫内膜癌复发的独立危险因素，高龄、低体重、高血压使Ⅰ~Ⅱ期子宫内膜癌的复发率增加（P < 0.05），见表 2。
表 2 影响Ⅰ~Ⅱ期子宫内膜癌复发的独立危险因素分析Table 2 Analysis of independent risk factors affecting recurrence of stage Ⅰ-Ⅱendometrial carcinoma
3 讨论
国内文献报道Ⅰ~Ⅱ期子宫内膜癌患者复发转移率在5.0%~18.0%[3]，对相关因素分析未做多因素分析，本研究516例Ⅰ~Ⅱ期子宫内膜癌患者发现复发46例，复发率为8.91%，与上述报道相符。既往研究多对Ⅰ~Ⅳ期子宫内膜癌患者整体研究，本研究主要对Ⅰ~Ⅱ期子宫内膜癌患者进行研究，排除肿瘤患者已有远处转移因素，从而减少复发因素研究的偏畸。
在国内外已有的子宫内膜癌预后分析相关因素文献报道中，大多数认为子宫内膜癌的预后可能与年龄、生育史、内科合并症、手术－病理分期、病理类型、组织学分级、肌层浸润、宫颈受累、淋巴结转移等因素有关[4-5]，但是文献报道的结果不一。本研究单因素分析中发现年龄、体重、血压、手术病理分期、病理类型、ER及PR表达与Ⅰ~Ⅱ期子宫内膜癌复发存在相关性。年龄、体重、血压是Ⅰ~Ⅱ期子宫内膜癌复发的风险因子，手术病理分期越高Ⅰ~Ⅱ期子宫内膜癌复发的风险增大；特殊类型的子宫内膜癌的Ⅰ~Ⅱ期患者复发风险随之增高；ER、PR在病理检查中表达越低复发风险越大。相关研究显示随ER、PR表达率降低，早期子宫内膜癌术后患者复发率增高，病理分期、病理分化程度、脉管癌栓以及肌层浸润或淋巴结转移率增加，进一步支持ER、PR的缺失与细胞恶性程度上升、侵袭性增加及向非激素依赖型肿瘤转化相关这一结论[6]。ER、PR的存在提示子宫内膜癌细胞对激素刺激有一定反应能力，也是内分泌抗雌激素治疗子宫内膜癌的理论基础，两者之一或同时缺失会导致肿瘤对激素治疗的效果不明显及预后不佳。
本次研究中病理分化程度、脉管转移及腹水细胞学异常与Ⅰ~Ⅱ期子宫内膜癌复发关系研究中未见明显差异，可能与以上有关高危因素患者术后已添加相关的辅助治疗，降低了复发风险，从而影响其复发结果；Ⅰ~Ⅱ期子宫内膜癌患者术中是否行淋巴结切除并未影响患者术后复发，可能与淋巴结转移并非是内膜癌转移唯一途径有关。虽然流行病学提示糖尿病是子宫内膜癌发病因素之一[7-8]，但是本次Ⅰ~Ⅱ期子宫内膜癌合并糖尿病患者研究未见明显的术后复发差异。
单因素分析及多因素分析证实年龄、体重、血压是Ⅰ~Ⅱ期子宫内膜癌复发的独立危险因素。年龄越大复发率越高；低体重及高血压Ⅰ~Ⅱ期子宫内膜癌术后复发率增加。可能随着年龄的增加，伴随体重的减轻，子宫内膜癌患者机体本身机能下降，术后恢复能力降低。Santeufemia等研究Ⅰ~Ⅳ期子宫内膜癌复发患者中发现，年龄大于60岁是子宫内膜癌患者复发的独立危险因素[9]，但其研究过程中未能有效排除Ⅲ~Ⅳ期患者自身对复发的影响。虽然肥胖是子宫内膜癌的发病因素之一[10-11]，也有报道指出肥胖与子宫内膜癌的复发有关[12]，然而最近Felix等对Ⅰ~Ⅲ期子宫内膜癌复发因素研究中提出低体重可能是影响因素之一，低体重子宫内膜癌患者中的复发风险增高[13]，在其研究中没有排除Ⅲ期子宫内膜癌中肿瘤远处转移的可能性及未提出其作为独立危险因素，但本次研究Ⅰ~Ⅱ期子宫内膜癌患者低体重既是相关影响因素同时也成为独立危险因素之一。流行病学调查显示高血压是子宫内膜癌发病因素之一[14]；随年龄增长高血压患病率上升，60岁前男性高血压的患病率普遍高于女性，之后女性的患病率逐渐增高超过男性，这可能与女性雌激素的保护有关[15]。本研究证实高血压是Ⅰ~Ⅱ期子宫内膜癌复发的相关影响因素，更是独立危险因素之一。可能高血压与Ⅰ~Ⅱ期子宫内膜癌复发患者存在相关分子机制相互影响，但还有待进一步研究。
本次研究中未将肿瘤的直径大小纳入研究对象，因为患者入院治疗前大多数行诊刮术或宫腔镜检查，检查后再手术时间长短影响肿瘤的直径大小。通过回顾性研究发现年龄、体重、高血压是Ⅰ~Ⅱ期子宫内膜癌复发独立危险因素，提示我们可从以上三方面进一步研究Ⅰ~Ⅱ期子宫内膜癌复发的机制。
Competing interests: The authors declare that they have no competing interests.利益冲突声明：所有作者均声明不存在利益冲突。作者贡献：刘汝贵、赵瑞瑞：总结和归纳文献、文章撰写刘春朝、武晓：文章选题、指导、审校 -
[1] Bade BC, Dela Cruz CS. Lung Cancer 2020 Epidemiology, Etiology, and Prevention[J]. Clin Chest Med, 2020, 41(1): 1-24. doi: 10.1016/j.ccm.2019.10.001
[2] Howlader N, Forjaz G, Mooradian MJ, et al. The Effect of Advances in Lung-Cancer Treatment on Population Mortality[J]. N Engl J Med, 2020, 383(7): 640-649. doi: 10.1056/NEJMoa1916623
[3] Gelatti ACZ, Drilon A, Santini FC. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC)[J]. Lung Cancer, 2019, 137: 113-122. doi: 10.1016/j.lungcan.2019.09.017
[4] Hayashi H, Nadal E, Gray JE, et al. Overall Treatment Strategy for Patients With Metastatic NSCLC With Activating EGFR Mutations[J]. Clin Lung Cancer, 2022, 23(1): E69-E82. doi: 10.1016/j.cllc.2021.10.009
[5] Leonetti A, Sharma S, Minari R, et al. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer[J]. Br J Cancer, 2019, 121(9): 725-737. doi: 10.1038/s41416-019-0573-8
[6] Yang J, Li YB, Sun JM, et al. An Osimertinib-Perfluorocarbon Nanoemulsion with Excellent Targeted Therapeutic Efficacy in Non-small Cell Lung Cancer: Achieving Intratracheal and Intravenous Administration[J]. ACS Nano, 2022, 16(8): 12590-12605. doi: 10.1021/acsnano.2c04159
[7] Khan KU, Minhas MU, Badshah SF, et al. Overview of nanoparticulate strategies for solubility enhancement of poorly soluble drugs[J]. Life Sci, 2022, 291: 120301. doi: 10.1016/j.lfs.2022.120301
[8] Peng SJ, Xiao FF, Chen MW, et al. Tumor-Microenvironment-Responsive Nanomedicine for Enhanced Cancer Immunotherapy[J]. Adv Sci, 2022, 9(1): 2103836. doi: 10.1002/advs.202103836
[9] Carcereny E, Moran T, Capdevila L, et al. The epidermal growth factor receptor (EGRF) in lung cancer[J]. Transl Respir Med, 2015, 3: 1. doi: 10.1186/s40247-015-0013-z
[10] Hassanein SS, Ibrahim SA, Abdel-Mawgood AL. Cell Behavior of Non-Small Cell Lung Cancer Is at EGFR and MicroRNAs Hands[J]. Int J Mol Sci, 2021, 22(22): 12496. doi: 10.3390/ijms222212496
[11] Da Cunha Santos G, Shepherd FA, Tsao MS. EGFR mutations and lung cancer[J]. Annu Rev Pathol, 2011, 6: 49-69. doi: 10.1146/annurev-pathol-011110-130206
[12] Uribe ML, Marrocco I, Yarden Y. EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance[J]. Cancers, 2021, 13(11): 2748. doi: 10.3390/cancers13112748
[13] Wu SG, Chang YL, Hsu YC, et al. Good Response to Gefitinib in Lung Adenocarcinoma of Complex Epidermal Growth Factor Receptor (EGFR) Mutations with the Classical Mutation Pattern[J]. Oncologist, 2008, 13(12): 1276-1284. doi: 10.1634/theoncologist.2008-0093
[14] Harrison PT, Vyse S, Huang PH. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer[J]. Semin Cancer Biol, 2020, 61: 167-179. doi: 10.1016/j.semcancer.2019.09.015
[15] Castellanos E, Feld E, Horn L. Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non-Small Cell Lung Cancer[J]. J Thorac Oncol, 2017, 12(4): 612-623. doi: 10.1016/j.jtho.2016.12.014
[16] Mithoowani H, Febbraro M. Non-Small-Cell Lung Cancer in 2022: A Review for General Practitioners in Oncology[J]. Curr Oncol, 2022, 29(3): 1828-1839. doi: 10.3390/curroncol29030150
[17] Ramalingam SS, Yang JCH, Lee CK, et al. Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer[J]. J Clin Oncol, 2018, 36(9): 841-849. doi: 10.1200/JCO.2017.74.7576
[18] Lu S, Dong X R, Jian H, et al. AENEAS: A Randomized Phase Ⅲ Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations[J]. J Clin Oncol, 2022, 40(27): 3162-3171. doi: 10.1200/JCO.21.02641
[19] Piper-Vallillo AJ, Sequist LV, Piotrowska Z. Emerging Treatment Paradigms for EGFR-Mutant Lung Cancers Progressing on Osimertinib: A Review[J]. J Clin Oncol, 2020, 38(25): 2926-2936. doi: 10.1200/JCO.19.03123
[20] Zeng Y, Yu DL, Tian WT, et al. Resistance mechanisms to osimertinib and emerging therapeutic strategies in nonsmall cell lung cancer[J]. Curr Opin Oncol, 2022, 34(1): 54-65. doi: 10.1097/CCO.0000000000000805
[21] He J, Huang Z, Han L, et al. Mechanisms and management of 3rd-generation EGFR-TKI resistance in advanced non-small cell lung cancer (Review)[J]. Int J Oncol, 2021, 59(5): 90. doi: 10.3892/ijo.2021.5270
[22] Liu Q, Yu S, Zhao W, et al. EGFR-TKIs resistance via EGFR-independent signaling pathways[J]. Mol Cancer, 2018, 17(1): 53. doi: 10.1186/s12943-018-0793-1
[23] Etheridge ML, Campbell SA, Erdman AG, et al. The big picture on nanomedicine: the state of investigational and approved nanomedicine products[J]. Nanomedicine, 2013, 9(1): 1-14. doi: 10.1016/j.nano.2012.05.013
[24] Ramasamy T, Ruttala HB, Gupta B, et al. Smart chemistry-based nanosized drug delivery systems for systemic applications: A comprehensive review[J]. J Control Release, 2017, 258. 226-253. doi: 10.1016/j.jconrel.2017.04.043
[25] Xu XY, Ho W, Zhang XQ, et al. Cancer nanomedicine: from targeted delivery to combination therapy[J]. Trends Mol Med, 2015, 21(4): 223-232. doi: 10.1016/j.molmed.2015.01.001
[26] Jahangirian H, Lemraski EG, Webster TJ, et al. A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine[J]. Int J Nanomedicine, 2017, 12. 2957-2978. doi: 10.2147/IJN.S127683
[27] Caster JM, Patel AN, Zhang T, et al. Investigational nanomedicines in 2016: a review of nanotherapeutics currently undergoing clinical trials[J]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2017, 9(1).
[28] Soejima K, Yasuda H, Hirano T. Osimertinib for EGFR T790M mutation-positive non-small cell lung cancer[J]. Expert Rev Clin Pharmacol, 2017, 10(1): 31-38. doi: 10.1080/17512433.2017.1265446
[29] Goss G, Tsai CM, Shepherd FA, et al. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study[J]. Lancet Oncol, 2016, 17(12): 1643-1652. doi: 10.1016/S1470-2045(16)30508-3
[30] Hu XC, Chen SM, Yin H, et al. Chitooligosaccharides-modified PLGA nanoparticles enhance the antitumor efficacy of AZD9291 (Osimertinib) by promoting apoptosis[J]. Int J Biol Macromol, 2020, 162: 262-272. doi: 10.1016/j.ijbiomac.2020.06.154
[31] Guardiola S, Sanchez-Navarro M, Rosell R, et al. Anti-EGF nanobodies enhance the antitumoral effect of osimertinib and overcome resistance in non-small cell lung cancer (NSCLC) cellular models[J]. Med Oncol, 2022, 39(12): 195. doi: 10.1007/s12032-022-01800-1
[32] Izci M, Maksoudian C, Manshian BB, et al. The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors[J]. Chem Rev, 2021, 121(3): 1746-1803. doi: 10.1021/acs.chemrev.0c00779
[33] Kang H, Rho S, Stiles WR, et al. Size-Dependent EPR Effect of Polymeric Nanoparticles on Tumor Targeting[J]. Adv Healthc Mater, 2020, 9(1): 1901223. doi: 10.1002/adhm.201901223
[34] Ulldemolins A, Seras-Franzoso J, Andrade F, et al. Perspectives of nano-carrier drug delivery systems to overcome cancer drug resistance in the clinics[J]. Cancer Drug Resist, 2021, 4(1): 44-68.
[35] Kaushik N, Borkar SB, Nandanwar SK, et al. Nanocarrier cancer therapeutics with functional stimuli-responsive mechanisms[J]. J Nanobiotechnol, 2022, 20(1): 152. doi: 10.1186/s12951-022-01364-2
[36] Kravanja G, Primozic M, Knez Z, et al. Chitosan-Based (Nano)Materials for Novel Biomedical Applications[J]. Molecules, 2019, 24(10): 960.
[37] Cao Y, Tan YF, Wong YS, et al. Recent Advances in Chitosan-Based Carriers for Gene Delivery[J]. Mar Drugs, 2019, 17(6): 381. doi: 10.3390/md17060381
[38] Kumar SK, Choppala AD. Development and Optimization of Osimertinib-loaded Biodegradable Polymeric Nanoparticles Enhance In-vitro Cytotoxicity in Mutant EGFR NSCLC Cell Models and In-vivo Tumor Reduction in H1975 Xenograft Mice Models[J]. Aaps Pharmscitech, 2022, 23(5): 159. doi: 10.1208/s12249-022-02314-9
[39] Gu JJ, Yao WL, Shi PY, et al. MEK or ERK inhibition effectively abrogates emergence of acquired osimertinib resistance in the treatment of epidermal growth factor receptor-mutant lung cancers[J]. Cancer, 2020, 126(16): 3788-3799. doi: 10.1002/cncr.32996
[40] Li YT, Zang HJ, Qian GQ, et al. ERK inhibition effectively overcomes acquired resistance of epidermal growth factor receptor-mutant non-small-cell lung cancer cells to osimertinib[J]. Cancer, 2020, 126(6): 1339-1350. doi: 10.1002/cncr.32655
[41] Chen W, Yu DL, Sun SY, et al. Nanoparticles for co-delivery of osimertinib and selumetinib to overcome osimertinib-acquired resistance in non-small cell lung cancer[J]. Acta Biomater, 2021, 129: 258-268. doi: 10.1016/j.actbio.2021.05.018
[42] Zhang QN, Yie GQ, Li Y, et al. Studies on the cyclosporin A loaded stearic acid nanoparticles[J]. Int J Pharm, 2000, 200(2): 153-159. doi: 10.1016/S0378-5173(00)00361-6
[43] Trombino S, Russo R, Mellace S, et al. Solid lipid nanoparticles made of trehalose monooleate for cyclosporin-A topic release[J]. J Drug Deliv Sci Technol, 2019, 49: 563-569. doi: 10.1016/j.jddst.2018.12.026
[44] Chen SM, Ji XG, Zhao MY, et al. Construction of chitooligosaccharide-based nanoparticles of pH/redox cascade responsive for co-loading cyclosporin A and AZD9291[J]. Carbohydr Polym, 2022, 291: 1119619.
[45] Chen Q, Huang GJ, Wu WT, et al. A Hybrid Eukaryotic-Prokaryotic Nanoplatform with Photothermal Modality for Enhanced Antitumor Vaccination[J]. Adv Mater, 2020, 32(16): 1908185. doi: 10.1002/adma.201908185
[46] Xu B, Zeng FJ, Deng JL, et al. A homologous and molecular dual-targeted biomimetic nanocarrier for EGFR-related non-small cell lung cancer therapy[J]. Bioact Mater, 2023, 27: 337-347.
[47] Ren MX, Li YZ, Zhang H, et al. An oligopeptide/aptamer-conjugated dendrimer-based nanocarrier for dual-targeting delivery to bone[J]. J Mat Chem B, 2021, 9(12): 2831-2844. doi: 10.1039/D0TB02926B
[48] Shen SH, Wu YS, Liu YC, et al. High drug-loading nanomedicines: progress, current status, and prospects[J]. Int J Nanomed, 2017, 12. 4085-4109. doi: 10.2147/IJN.S132780
[49] Vega-Villa KR, Takemoto JK, Yanez JA, et al. Clinical toxicities of nanocarrier systems[J]. Adv Drug Deliv Rev, 2008, 60(8): 929-938. doi: 10.1016/j.addr.2007.11.007
[50] Pingale P, Kendre P, Pardeshi K, et al. An emerging era in manufacturing of drug delivery systems: Nanofabrication techniques[J]. Heliyon, 2023, 9(3): e14247. doi: 10.1016/j.heliyon.2023.e14247
[51] Huang L, Zhao SJ, Fang F, et al. Advances and perspectives in carrier-free nanodrugs for cancer chemo-monotherapy and combination therapy[J]. Biomaterials, 2021, 268. 120557. doi: 10.1016/j.biomaterials.2020.120557
[52] Yang MY, Zhao RR, Fang YF, et al. Carrier-free nanodrug: A novel strategy of cancer diagnosis and synergistic therapy[J]. Int J Pharm, 2019, 570: 118663. doi: 10.1016/j.ijpharm.2019.118663
[53] Liu LH, Zhang XZ. Carrier-free nanomedicines for cancer treatment[J]. Prog Mater Sci, 2022, 125: 100919. doi: 10.1016/j.pmatsci.2021.100919
[54] Fu SW, Li GT, Zang WL, et al. Pure drug nano-assemblies: A facile carrier-free nanoplatform for efficient cancer therapy[J]. Acta Pharm Sin B, 2022, 12(1): 92-106. doi: 10.1016/j.apsb.2021.08.012
[55] Mei H, Cai SS, Huang DN, et al. Carrier-free nanodrugs with efficient drug delivery and release for cancer therapy: From intrinsic physicochemical properties to external modification[J]. Bioact Mater, 2022, 8: 220-240.
[56] Han HS, Choi KY. Advances in Nanomaterial-Mediated Photothermal Cancer Therapies: Toward Clinical Applications[J]. Biomedicines, 2021, 9(3): 305. doi: 10.3390/biomedicines9030305
[57] Correia JH, Rodrigues JA, Pimenta S, et al. Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions[J]. Pharmaceutics, 2021, 13(9): 1332. doi: 10.3390/pharmaceutics13091332
[58] Yang L, Huang B, Hu SQ, et al. Indocyanine green assembled free oxygen-nanobubbles towards enhanced near-infrared induced photodynamic therapy[J]. Nano Res, 2022, 15(5): 4285-4293. doi: 10.1007/s12274-022-4085-0
[59] Hu XY, Li JW, Chen YL, et al. A Self-Assembly ICG Nanoparticle Potentiating Targeted Photothermal and Photodynamic Therapy in NSCLC[J]. ACS Biomater Sci Eng, 2022, 8(10): 4535-4546. doi: 10.1021/acsbiomaterials.2c00620
下载:
计量
- 文章访问数: 1201
- HTML全文浏览量: 2228
- PDF下载量: 1226
