超声介导的雷公藤甲素外泌体靶向给药系统抗结直肠癌的应用评估

doi:10.3877/cma.j.issn.2095-2015.2026.01.003

目的

构建结直肠癌患者来源肿瘤异种移植（CRC-PDX）模型，体内评估超声（US）介导的雷公藤甲素（TPL）外泌体给药系统的安全性及抗肿瘤效果。

方法

回顾性收集2024年3月至2025年3月于郴州市第一人民医院接受过手术治疗的100例结直肠癌患者肿瘤组织，构建CRC-PDX模型，其中1例晚期恶性患者来源的CRC-PDX模型传代至F3代；采用电穿孔法将TPL转载至人脐带间充质干细胞（huc-MSCs）外泌体（sEVs）制备TPL@sEVs；通过Western Blot和高效液相色谱法对其进行表征；将F3代模型裸鼠随机分成6组（n=6）：对照组（PBS）、sEVs组、US＋sEVs组、TPL@sEVs组、US＋TPL@sEVs组和5-氟尿嘧啶（5-FU）组，通过尾静脉给药，评估给药系统安全性及抑瘤效果。

结果

本研究共纳入100例结直肠癌患者，P0代CRC-PDX模型成瘤率为62%（57/92），原发肿瘤部位、TNM分期及术前癌胚抗原水平是成瘤的影响因素（P<0.05）；F3代CRC-PDX肿瘤组织与原发肿瘤在细胞结构、低氧诱导因子-1α（HIF-1α）/核因子κB（NF-κB）/ Ki-67蛋白表达上高度一致；表征结果显示，成功构建了载药量为（12.77±1.65）%的TPL@sEVs；给药系统安全性评估显示，仅5-FU组裸鼠出现轻度腹泻、食欲减退，且肝脏系数、脾脏系数显著低于对照组（P<0.05）；TPL@sEVs组的ALT、AST、CRE等肝肾功能指标相较于对照组显著异常（P<0.05），而US＋TPL@sEVs组上述指标较TPL@sEVs组明显改善（P<0.05）；给药系统抗肿瘤效果评估显示，与对照组相比，所有处理组的肿瘤体积与质量均显著降低（P<0.05），其中US＋TPL@sEVs组的抑制效果最佳；免疫组化显示，与对照组相比，所有处理组的HIF-1α/NF-κB/Ki-67蛋白表达均有一定程度的下调，其中US＋TPL@sEVs组对HIF-1α/NF-κB的蛋白表达抑制作用显著强于5-FU组（P<0.05），对Ki-67的蛋白抑制与5-FU组差异无统计学意义（P>0.05）。

结论

超声介导的TPL外泌体靶向给药系统可显著降低TPL的毒副作用，增强对CRC-PDX模型的抗肿瘤活性，是一种具有潜力的结直肠癌靶向治疗策略。

关键词: 结直肠癌, 雷公藤甲素, 外泌体, 超声介导

Objective

To establish a patient-derived xenograft model of colorectal cancer (CRC-PDX) and evaluate the safety and anti-tumor efficacy of an ultrasound (US)-mediated triptolide (TPL)-loaded exosome delivery system in vivo.

Methods

Tumor tissues were retrospectively collected from 100 CRC patients who underwent surgical treatment in Chenzhou First People's Hospital from March 2024 to March 2025 for the establishment of CRC-PDX models. Among these, the CRC-PDX model derived from one patient with advanced malignant CRC was passaged to the F3 generation. TPL was loaded into exosomes (sEVs) isolated from human umbilical cord mesenchymal stem cells (huc-MSCs) via electroporation to prepare TPL@sEVs, which were characterized by Western Blot and high-performance liquid chromatography. F3-generation model nude mice were randomly divided into 6 groups (n=6): control (PBS), sEVs, US+sEVs, TPL@sEVs, US+TPL@sEVs, and 5-Fu groups. The safety and anti-tumor effects of the delivery system were evaluated after administration via tail vein injection.

Results

A total of 100 CRC patients were included in this study. The tumor formation rate of the P0-generation CRC-PDX models was 62% (57/92). Primary tumor location, TNM stage, and preoperative carcino-embryonic antigen level were identified as influencing factors for tumor formation (P<0.05). The F3-generation CRC-PDX tumor tissues were highly consistent with the primary tumor in terms of cell structure and protein expressions of hypoxia-inducible factor-1α (HIF-1α)/Nuclear factor κB (NF-κB)/Ki-67. Characterization results confirmed that the successful preparation of TPL@sEVs with a drug loading capacity of (12.77± 1.65)%. Safety assessment of the delivery system showed that only nude mice in the 5-Fu group exhibited mild diarrhea and transient anorexia, with significantly lower liver and spleen coefficients than those in the control group (P<0.05). The TPL@sEVs group showed significant abnormalities in liver and kidney function indicators (such as ALT, AST, and CRE) compared with the control group (P<0.05), while these indicators in the US+TPL@sEVs group were significantly improved compared with the TPL@sEVs group (P<0.05). Anti-tumor efficacy assessment revealed that compared with the control group, all treatment groups showed significantly reduced tumor volume and weight (P<0.05), with the US+TPL@sEVs group exhibiting the best inhibitory effect. Immunohistochemical results indicated that compared with the control group, all treatment groups showed a certain degree of downregulation in the protein expressions of HIF-1α/NF-κB/Ki-67. Specifically, the US+TPL@sEVs group had a significantly stronger inhibitory effect on the protein expressions of HIF-1α/NF-κB than the 5-Fu group (P<0.05), while there was no significant difference in the inhibitory effect on Ki-67 protein expression between the US+TPL@sEVs group and the 5-Fu group (P>0.05).

Conclusion

The US-mediated TPL-loaded exosome targeted delivery system can significantly reduce the toxic and side effects of TPL and enhance the anti-tumor activity against the CRC-PDX model, making it a promising targeted therapeutic strategy for colorectal cancer.

Key words: Colorectal cancer, Triptolide, Exosomes, Ultrasound-mediated

表1 用于构建结直肠癌患者来源肿瘤异种移植模型的患者的一般特征

临床参数	例数(n=92)	成瘤性		χ²/t值	P值
临床参数	例数(n=92)	是(n=57)	否(n=35)	χ²/t值	P值
年龄(岁,±s)	60.70±12.51	59.70±11.72	62.30±13.42	-0.98	0.328
性别[例(%)]				2.88	0.090
女	22(23.91)	17(29.82)	5(14.29)
男	70(76.08)	40(70.18)	30(85.71)
肿瘤部位[例(%)]				13.89	<0.001
左半结肠	18(19.56)	13(72.22)	5(27.78)
右半结肠	35(38.04)	28(80.00)	7(20.0)
直肠	39(42.39)	16(41.02)	23(58.97)
TNM分期[例(%)]				14.37	<0.001
Ⅰ期	14(15.22)	5(35.71)	9(64.29)
Ⅱ期	23(25.00)	12(52.17)	11(47.83)
Ⅲ期	27(29.34)	15(55.56)	12(44.44)
Ⅳ期	28(30.43)	25(89.29)	3(10.71)
术前癌胚抗原水平[例(%)]				22.18	<0.001
<10 ng/mL	53(57.61)	22(41.51)	31(58.50)
≥10 ng/mL	39(42.40)	35(89.74)	4(10.26)

表1 用于构建结直肠癌患者来源肿瘤异种移植模型的患者的一般特征

临床参数	例数(n=92)	成瘤性		χ²/t值	P值
临床参数	例数(n=92)	是(n=57)	否(n=35)	χ²/t值	P值
年龄(岁,±s)	60.70±12.51	59.70±11.72	62.30±13.42	-0.98	0.328
性别[例(%)]				2.88	0.090
女	22(23.91)	17(29.82)	5(14.29)
男	70(76.08)	40(70.18)	30(85.71)
肿瘤部位[例(%)]				13.89	<0.001
左半结肠	18(19.56)	13(72.22)	5(27.78)
右半结肠	35(38.04)	28(80.00)	7(20.0)
直肠	39(42.39)	16(41.02)	23(58.97)
TNM分期[例(%)]				14.37	<0.001
Ⅰ期	14(15.22)	5(35.71)	9(64.29)
Ⅱ期	23(25.00)	12(52.17)	11(47.83)
Ⅲ期	27(29.34)	15(55.56)	12(44.44)
Ⅳ期	28(30.43)	25(89.29)	3(10.71)
术前癌胚抗原水平[例(%)]				22.18	<0.001
<10 ng/mL	53(57.61)	22(41.51)	31(58.50)
≥10 ng/mL	39(42.40)	35(89.74)	4(10.26)

图1 CRC-PDX移植瘤组织（P0~F3代）与原发肿瘤组织（P代)免疫组化结果比较注：CRC-PDX结直肠癌患者来源肿瘤异种移植；HIF-1α低氧诱导因子-1α；NF-κB核因子κB

图2 TPL@sEVs的表征与载药效率优化注：2A为Western Blot鉴定外泌体标志蛋白；2B为基于不同投料比的载药效率筛选。sEVs为外泌体；TPL为雷公藤甲素

表2 结直肠癌患者来源肿瘤异种移植模型裸鼠经多种给药处理后各脏器系数对照表（n=6，

±s）

脏器	对照组	sEVs组	US+sEVs组	TPL@sEVs组	US+TPL@sEVs组	5-FU组	F值	P值
心	5.19±0.61	5.30±0.64	5.21±0.81	5.51±0.63	5.42±0.61	5.50±0.84	0.84	0.532
肝	48.01±4.82	47.51±5.20	47.81±4.62	47.00±5.53	48.58±4.60	45.21±5.10^*	4.27	0.005
脾	3.01±0.43	2.81±0.42	3.09±0.44	3.20±0.29	2.85±0.43	2.06±0.30^*	8.95	<0.001
肺	6.52±0.90	6.61±1.04	6.50±0.81	6.71±0.88	6.61±1.27	6.75±1.20	0.32	0.896
肾	12.03±1.50	11.72±1.29	12.22±1.80	11.47±1.52	11.60±1.32	11.48±1.81	1.05	0.406

表2 结直肠癌患者来源肿瘤异种移植模型裸鼠经多种给药处理后各脏器系数对照表（n=6，

±s）

脏器	对照组	sEVs组	US+sEVs组	TPL@sEVs组	US+TPL@sEVs组	5-FU组	F值	P值
心	5.19±0.61	5.30±0.64	5.21±0.81	5.51±0.63	5.42±0.61	5.50±0.84	0.84	0.532
肝	48.01±4.82	47.51±5.20	47.81±4.62	47.00±5.53	48.58±4.60	45.21±5.10^*	4.27	0.005
脾	3.01±0.43	2.81±0.42	3.09±0.44	3.20±0.29	2.85±0.43	2.06±0.30^*	8.95	<0.001
肺	6.52±0.90	6.61±1.04	6.50±0.81	6.71±0.88	6.61±1.27	6.75±1.20	0.32	0.896
肾	12.03±1.50	11.72±1.29	12.22±1.80	11.47±1.52	11.60±1.32	11.48±1.81	1.05	0.406

表3 结直肠癌患者来源肿瘤异种移植模型裸鼠经多种给药处理后临床生化指标对照表（n=6，

±s）

参数	对照组	sEVs组	US+sEVs组	TPL@sEVs组	US+TPL@sEVs组	5-FU组	F值	P值
ALT(U/L)	45.13±11.92	45.10±10.23	40.25±10.17	80.05±15.35^#	59.73±12.00^*	150.15±20.34^#	62.85	<0.001
AST(U/L)	50.40±10.05	59.75±15.33	50.10±15.06	105.19±15.48^#	70.27±10.40^#*	198.78±20.07^#	98.42	<0.001
碱性磷酸酶(U/L)	100.24±20.13	110.14±15.29	100.04±10.37	160.01±20.22^#	110.27±30.23^*	270.19±29.68^#	91.57	<0.001
总胆红素(μmol/L)	4.27±2.16	4.08±1.75	3.06±2.40	9.32±2.06^#	5.11±1.97^*	16.90±2.85^#	78.36	<0.001
白蛋白(g/L)	37.08±3.38	35.75±2.36	37.33±3.35	30.33±2.07^#	33.37±2.78^#	23.15±2.33^#	69.14	<0.001
尿素氮(mmol/L)	6.23±2.14	7.00±1.27	6.33±1.47	10.15±2.10^#	6.79±2.11^*	17.24±3.00^#	73.52	<0.001
肌酐(μmol/L)	25.02±5.13	29.67±5.09	25.24±5.10	55.15±10.43^#	35.33±9.67^#*	90.08±10.38^#	86.93	<0.001

表3 结直肠癌患者来源肿瘤异种移植模型裸鼠经多种给药处理后临床生化指标对照表（n=6，

±s）

参数	对照组	sEVs组	US+sEVs组	TPL@sEVs组	US+TPL@sEVs组	5-FU组	F值	P值
ALT(U/L)	45.13±11.92	45.10±10.23	40.25±10.17	80.05±15.35^#	59.73±12.00^*	150.15±20.34^#	62.85	<0.001
AST(U/L)	50.40±10.05	59.75±15.33	50.10±15.06	105.19±15.48^#	70.27±10.40^#*	198.78±20.07^#	98.42	<0.001
碱性磷酸酶(U/L)	100.24±20.13	110.14±15.29	100.04±10.37	160.01±20.22^#	110.27±30.23^*	270.19±29.68^#	91.57	<0.001
总胆红素(μmol/L)	4.27±2.16	4.08±1.75	3.06±2.40	9.32±2.06^#	5.11±1.97^*	16.90±2.85^#	78.36	<0.001
白蛋白(g/L)	37.08±3.38	35.75±2.36	37.33±3.35	30.33±2.07^#	33.37±2.78^#	23.15±2.33^#	69.14	<0.001
尿素氮(mmol/L)	6.23±2.14	7.00±1.27	6.33±1.47	10.15±2.10^#	6.79±2.11^*	17.24±3.00^#	73.52	<0.001
肌酐(μmol/L)	25.02±5.13	29.67±5.09	25.24±5.10	55.15±10.43^#	35.33±9.67^#*	90.08±10.38^#	86.93	<0.001

图3 CRC-PDX模型裸鼠经多种给药处理后肿瘤体积和质量的变化注：3A肿瘤体积；3B肿瘤质量。与Control组比较，^*P<0.05；与TPL@sEVs组比较，^P<0.05；与5-FU组比较，^#P<0.05。CRC-PDX结直肠癌患者来源肿瘤异种移植；sEVs为外泌体；US＋sEVs为超声介导的外泌体；TPL@sEVs为装载雷公藤甲素的外泌体；US＋TPL@sEVs为超声介导的装载雷公藤甲素的外泌体；5-FU为5-氟尿嘧啶

图4 CRC-PDX模型裸鼠不同方案处理后肿瘤组织特征蛋白表达的变化注：4A为HIF-1α蛋白表达水平；4B为Ki-67蛋白表达水平；4C为NF-κB蛋白表达水平；与Control比较，^*P<0.05；与TPL@sEVs组比较，^P<0.05；与5-FU组比较，^#P<0.05。CRC-PDX为结直肠癌患者来源肿瘤异种移植；sEVs为外泌体；US＋sEVs为超声介导的外泌体；TPL@sEVs为装载雷公藤甲素的外泌体；US＋TPL@sEVs为超声介导的装载雷公藤甲素的外泌体；5-FU为5-氟尿嘧啶

表4 CRC-PDX模型裸鼠经多种给药处理后肿瘤体积和质量的变化（n=6，

±s）

组别	肿瘤体积(mm³)	肿瘤质量(g)
对照组	2483.33±275.38	1.53±0.15
sEVs组	1883.33±104.08	1.16±0.15
US+sEVs组	1600.00±100.00	0.91±0.10
TPL@sEVs组	1300.00±200.00	0.73±0.15
US+TPL@sEVs组	1066.67±152.75	0.47±0.06
5-FU组	1233.33±251.66	0.78±0.07
F值	28.63	32.47
P值	<0.001	<0.001

表4 CRC-PDX模型裸鼠经多种给药处理后肿瘤体积和质量的变化（n=6，

±s）

组别	肿瘤体积(mm³)	肿瘤质量(g)
对照组	2483.33±275.38	1.53±0.15
sEVs组	1883.33±104.08	1.16±0.15
US+sEVs组	1600.00±100.00	0.91±0.10
TPL@sEVs组	1300.00±200.00	0.73±0.15
US+TPL@sEVs组	1066.67±152.75	0.47±0.06
5-FU组	1233.33±251.66	0.78±0.07
F值	28.63	32.47
P值	<0.001	<0.001

[1]	Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024[J]. CA Cancer J Clin, 2024, 74(1): 12-49.
[2]	Siegel RL, Wagle NS, Cercek A, et al. Colorectal cancer statistics, 2023[J]. CA Cancer J Clin, 2023, 73(3): 233-254.
[3]	Zhu W, Li Y, Zhao J, et al. The mechanism of triptolide in the treatment of connective tissue disease-related interstitial lung disease based on network pharmacology and molecular docking[J]. Ann Med, 2022, 54(1): 541-552.
[4]	李传明, 徐婉丽, 沈艳. 雷公藤甲素通过调节miR-181b- 5p/SMAD2抑制结直肠癌细胞的增殖和转移[J]. 辽宁中医杂志, 2024, 51(3): 143-146.
[5]	郎晓雪, 薛剑桥, 付京, 等. 雷公藤甲素及其纳米制剂抗肿瘤作用研究进展[J]. 中国新药杂志, 2023, 32(9): 893-901.
[6]	Edwards IA, De Carlo F, Sitta J, et al. Enhancing Targeted Therapy in Breast Cancer by Ultrasound-Responsive Nanocarriers[J]. Int J Mol Sci, 2023, 24(6): 5474.
[7]	Terasaki M, Tsuruoka K, Tanaka T, et al. Fucoxanthin Inhibits Development of Sigmoid Colorectal Cancer in a PDX Model With Alterations of Growth, Adhesion, and Cell Cycle Signals[J]. Cancer Genomics Proteomics, 2023, 20(6suppl): 686-705.
[8]	Hu W, Yang Y, Li X, et al. Multi-omics Approach Reveals Distinct Differences in Left- and Right-Sided Colon Cancer[J]. Mol Cancer Res, 2018, 16(3): 476-485.
[9]	Yang Q, Qu R, Lu S, et al. Biological and Clinical Characteristics of Proximal Colon Cancer: Far from Its Anatomical Subsite[J]. Int J Med Sci, 2024, 21(10): 1824-1839.
[10]	Liu J, Shen M, Yue Z, et al. Triptolide inhibits colon-rectal cancer cells proliferation by induction of G1 phase arrest through upregulation of p21[J]. Phytomedicine, 2012, 19(8-9): 756-762.
[11]	Liskova V, Kajsik M, Chovancova B, et al. Camptothecin, triptolide, and apoptosis inducer kit have differential effects on mitochondria in colorectal carcinoma cells[J]. FEBS Open Bio, 2022, 12(5): 913-924.
[12]	Song X, He H, Zhang Y, et al. Mechanisms of action of triptolide against colorectal cancer: insights from proteomic and phosphoproteomic analyses[J]. Aging(Albany NY), 2022, 14(7): 3084-3104.
[13]	张美蓉, 张競, 张永刚, 等. 雷公藤甲素调节PI3K/Akt信号通路抑制结肠癌增殖并诱导凋亡的实验研究[J]. 临床肿瘤学杂志, 2021, 26(6): 506-511.
[14]	Liu J, Ren L, Li S, et al. The biology, function, and applications of exosomes in cancer[J]. Acta Pharm Sin B, 2021, 11(9): 2783-2797.
[15]	李香影, 刚乔健, 牟力圆, 等. 脐带间充质干细胞外泌体在肿瘤治疗中的研究进展[J]. 实用临床医药杂志, 2022, 26(23): 108-112+118.
[16]	Guo G, Tan Z, Liu Y, et al. The therapeutic potential of stem cell-derived exosomes in the ulcerative colitis and colorectal cancer[J]. Stem Cell Res Ther, 2022, 13(1): 138.
[17]	Li D, Lin F, Li G, et al. Exosomes derived from mesenchymal stem cells curbs the progression of clear cell renal cell carcinoma through T-cell immune response[J]. Cytotechnology, 2021, 73(4): 593-604.
[18]	Wang D, Wan Z, Yang Q, et al. Sonodynamical reversion of immunosuppressive microenvironment in prostate cancer via engineered exosomes[J]. Drug Deliv, 2022, 29(1): 702-713.
[19]	Liu X, Xin Z, Wang K. Patient-derived xenograft model in colorectal cancer basic and translational research[J]. Animal Model Exp Med, 2023, 6(1): 26-40.
[20]	Qiu D, Zhao G, Aoki Y, et al. Immunosuppressant PG490(triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/ nuclear factor of activated T-cells and NF-kappaB transcriptional activation[J]. J Biol Chem, 1999, 274(19): 13443-13450.
[21]	Brockmueller A, Girisa S, Motallebi M, et al. Calebin A targets the HIF-1α/NF-κB pathway to suppress colorectal cancer cell migration [J]. Front Pharmacol, 2023, 14: 1203436.
[22]	陈志, 鲍刚, 吴沁航, 等. 雷公藤甲素诱导结肠癌细胞凋亡的分子机制研究[J]. 时珍国医国药, 2019, 30(10): 2365-2367.
[23]	Ten Hoorn S, de Back TR, Sommeijer DW, et al. Clinical Value of Consensus Molecular Subtypes in Colorectal Cancer: A Systematic Review and Meta-Analysis[J]. J Natl Cancer Inst, 2022, 114(4): 503-516.

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Application evaluation of ultrasound-mediated targeted drug delivery system of triptolide exosomes in colorectal cancer

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Application evaluation of ultrasound-mediated targeted drug delivery system of triptolide exosomes in colorectal cancer