Advancing Bioconjugated Quantum Dots with Click Chemistry and Artificial Intelligence to Image and Treat Glioblastoma.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Quantum Dots*/chemistry ; Quantum Dots*/therapeutic use ; Glioblastoma*/diagnostic imaging ; Glioblastoma*/therapy ; Click Chemistry*/methods ; Brain Neoplasms*/diagnostic imaging ; Brain Neoplasms*/therapy ; Artificial Intelligence*; Humans ; Animals ; Drug Delivery Systems

Glioblastoma (GB) is one of the most aggressive and invasive cancers. Current treatment protocols for GB include surgical resection, radiotherapy, and chemotherapy with temozolomide. However, despite these treatments, physicians still struggle to effectively image, diagnose, and treat GB. As such, patients frequently experience recurrence of GB, demanding innovative strategies for early detection and effective therapy. Bioconjugated quantum dots (QDs) have emerged as powerful nanoplatforms for precision imaging and targeted drug delivery due to their unique optical properties, tunable size, and surface versatility. Due to their extremely small size, QDs can cross the blood-brain barrier and be used for precision imaging of GB. This review explores the integration of QDs with click chemistry for robust bioconjugation, focusing on artificial intelligence (AI) to advance GB therapy, mechanistic insights into cellular uptake and signaling, and strategies for mitigating toxicity. Click chemistry enables site-specific and stable conjugation of targeting ligands, peptides, and therapeutic agents to QDs, enhancing selectivity and functionalization. Algorithms driven by AI may facilitate predictive modeling, image reconstruction, and personalized treatment planning, optimizing QD design and therapeutic outcomes. We discuss molecular mechanisms underlying interactions of QDs with GB, including receptor-mediated endocytosis and intracellular trafficking, which influence biodistribution and therapeutic efficacy. Use of QDs in photodynamic therapy, which uses reactive oxygen species to induce apoptotic cell death in GB cells, is an innovative therapy that is covered in this review. Finally, this review addresses concerns associated with the toxicity of metal-based QDs and highlights how QDs can be coupled with AI to develop new methods for precision imaging for detecting and treating GB for induction of apoptosis. By converging nanotechnology and computational intelligence, bioconjugated QDs represent a transformative platform for paving a safer path to smarter and more effective clinical interventions of GB.

Int J Mol Sci. 2022 Mar 14;23(6):. (PMID: 35328538)
Adv Exp Med Biol. 2012;729:14-28. (PMID: 22411311)
Mol Cancer. 2023 Oct 9;22(1):169. (PMID: 37814270)
ACS Nano. 2022 Jun 28;16(6):9130-9141. (PMID: 35584060)
Methods Mol Biol. 2020;2135:95-108. (PMID: 32246330)
Angew Chem Int Ed Engl. 2001 Jun 1;40(11):2004-2021. (PMID: 11433435)
Neurooncol Pract. 2023 Oct 03;11(1):36-45. (PMID: 38222046)
Nat Commun. 2024 Aug 28;15(1):7455. (PMID: 39198451)
Acc Chem Res. 2018 Jun 19;51(6):1404-1414. (PMID: 29733571)
Nat Commun. 2023 Jan 26;14(1):435. (PMID: 36702831)
Nanotechnology. 2008 Jan 23;19(3):035701. (PMID: 21817586)
J Chem Inf Model. 2025 Mar 24;65(6):2773-2784. (PMID: 40036481)
Commun Biol. 2021 Feb 16;4(1):214. (PMID: 33594275)
Materials (Basel). 2019 Apr 11;12(7):. (PMID: 30978917)
Small. 2023 Oct;19(41):e2302195. (PMID: 37300352)
Bioconjug Chem. 2020 Mar 18;31(3):861-874. (PMID: 32083851)
Indian J Microbiol. 2025 Mar;65(1):424-438. (PMID: 40371036)
Colloids Surf B Biointerfaces. 2024 Feb;234:113721. (PMID: 38176338)
Acta Pharm Sin B. 2024 Mar;14(3):1111-1131. (PMID: 38486983)
Cells. 2023 Mar 15;12(6):. (PMID: 36980238)
Oncotarget. 2018 Apr 20;9(30):20993-21006. (PMID: 29765515)
Molecules. 2025 Jun 06;30(12):. (PMID: 40572449)
Int J Mol Sci. 2020 Aug 31;21(17):. (PMID: 32878114)
Colloids Surf B Biointerfaces. 2021 Mar;199:111549. (PMID: 33388720)
Magn Reson Med Sci. 2018 Jan 10;17(1):50-57. (PMID: 28638001)
Adv Mater. 2018 Nov;30(45):e1801350. (PMID: 30066341)
Pharmaceuticals (Basel). 2021 Mar 08;14(3):. (PMID: 33800301)
ACS Nano. 2013 Aug 27;7(8):7303-10. (PMID: 23841561)
J Neuroinflammation. 2023 Oct 19;20(1):237. (PMID: 37858199)
Front Immunol. 2023 Dec 07;14:1259797. (PMID: 38130720)
Front Neuroimaging. 2025 Oct 23;4:1630245. (PMID: 41210079)
RSC Adv. 2019 Apr 17;9(22):12218-12225. (PMID: 35515837)
Cell Death Dis. 2025 Apr 19;16(1):317. (PMID: 40253386)
Nat Commun. 2023 Feb 11;14(1):771. (PMID: 36774352)
BMC Cancer. 2021 Jan 12;21(1):54. (PMID: 33430813)
ACS Appl Bio Mater. 2022 Mar 21;5(3):1169-1178. (PMID: 35191305)
J Mater Chem B. 2016 Jun 21;4(23):4110-4118. (PMID: 32264613)
Discov Nano. 2023 Sep 8;18(1):111. (PMID: 37682347)
J Mater Chem B. 2024 May 8;12(18):4307-4334. (PMID: 38595268)
ACS Nano. 2022 Feb 22;16(2):1999-2012. (PMID: 35107994)
Chem Sci. 2021 Jul 6;12(31):10426-10435. (PMID: 34447534)
PLoS One. 2016 Jul 07;11(7):e0158537. (PMID: 27388765)
Res Pharm Sci. 2022 Sep 08;17(5):527-539. (PMID: 36386487)
Colloids Surf B Biointerfaces. 2025 Feb;246:114398. (PMID: 39608308)
Pharmaceutics. 2022 May 13;14(5):. (PMID: 35631639)
Pharm Res. 2016 Oct;33(10):2337-57. (PMID: 27207272)
Sci Rep. 2018 Jul 23;8(1):11093. (PMID: 30038284)
Adv Mater. 2023 Apr;35(15):e2210809. (PMID: 36740642)
Transl Cancer Res. 2022 Nov;11(11):4079-4088. (PMID: 36523299)
Biomedicines. 2024 Oct 10;12(10):. (PMID: 39457617)
Cancers (Basel). 2025 Mar 04;17(5):. (PMID: 40075725)
Biomaterials. 2022 Dec;291:121875. (PMID: 36335717)
ChemSusChem. 2024 Jul 8;17(13):e202301462. (PMID: 38433108)
J Appl Toxicol. 2024 Jul;44(7):936-952. (PMID: 38062852)
Bioconjug Chem. 2010 Apr 21;21(4):583-8. (PMID: 20222737)
Colloids Surf B Biointerfaces. 2021 Dec;208:112140. (PMID: 34597939)
Heliyon. 2023 Feb 02;9(2):e13422. (PMID: 36820041)
Nanomedicine (Lond). 2024;19(29):2433-2435. (PMID: 39344871)
Nanotoxicology. 2014 Dec;8(8):885-93. (PMID: 24040866)
Int J Clin Exp Pathol. 2015 Jul 01;8(7):7798-808. (PMID: 26339344)
ACS Appl Mater Interfaces. 2017 Nov 22;9(46):39901-39906. (PMID: 29120160)
Langmuir. 2017 Oct 3;33(39):10259-10270. (PMID: 28874049)
Rep Pract Oncol Radiother. 2022 Dec 29;27(6):1026-1036. (PMID: 36632307)
Adv Healthc Mater. 2014 Jan;3(1):10-29. (PMID: 23949967)
Cancer Lett. 2025 Apr 01;614:217536. (PMID: 39924081)
Chem Rev. 2021 Nov 10;121(21):13454-13619. (PMID: 34582186)
Cancer Med. 2024 Jan;13(2):e6800. (PMID: 38349028)
J Appl Toxicol. 2022 Jul;42(7):1218-1229. (PMID: 35083762)
Spectrochim Acta A Mol Biomol Spectrosc. 2023 Dec 15;303:123173. (PMID: 37499470)
Front Cell Infect Microbiol. 2025 Apr 16;15:1555617. (PMID: 40308970)
Chemistry. 2014 May 5;20(19):5640-8. (PMID: 24677275)
Environ Health Perspect. 2006 Feb;114(2):165-72. (PMID: 16451849)
Interface Focus. 2016 Dec 6;6(6):20160064. (PMID: 27920898)
Oncogenesis. 2020 Feb 5;9(2):11. (PMID: 32024816)
J Am Chem Soc. 2016 Dec 21;138(50):16478-16485. (PMID: 27936742)
Pharmacol Res. 2023 Mar;189:106694. (PMID: 36775082)
Nat Genet. 2021 Oct;53(10):1469-1479. (PMID: 34594037)
Annu Rev Biochem. 2018 Jun 20;87:871-896. (PMID: 29661000)
Coord Chem Rev. 2016 Aug 1;320-321:216-237. (PMID: 28344357)
Curr Probl Dermatol. 2021;55:374-384. (PMID: 34698043)
Bioconjug Chem. 2020 May 20;31(5):1497-1509. (PMID: 32337973)
Annu Rev Anal Chem (Palo Alto Calif). 2013;6:143-62. (PMID: 23527547)
Brief Bioinform. 2025 Nov 1;26(6):. (PMID: 41405959)
Biomed Pharmacother. 2024 Dec;181:117634. (PMID: 39489121)
Nano Lett. 2006 Apr;6(4):669-76. (PMID: 16608262)
Int J Nanomedicine. 2020 May 06;15:3217-3233. (PMID: 32440120)
Bioorg Med Chem Lett. 2019 Jul 1;29(13):1580-1585. (PMID: 31078409)
Nanomaterials (Basel). 2024 Jun 25;14(13):. (PMID: 38998691)
Nat Protoc. 2015 Jun;10(6):859-74. (PMID: 25974095)
Nanoscale Adv. 2021 May 31;3(13):3942-3953. (PMID: 34263140)
Adv Drug Deliv Rev. 2017 Jan 1;108:25-38. (PMID: 27137110)
ACS Biomater Sci Eng. 2017 Aug 14;3(8):1836-1844. (PMID: 33429665)
Cell Biosci. 2024 Sep 27;14(1):123. (PMID: 39334448)
Biochim Biophys Acta Biomembr. 2022 Apr 1;1864(4):183857. (PMID: 34990591)
Front Oncol. 2024 Aug 14;14:1409519. (PMID: 39206155)
Mater Sci Eng C Mater Biol Appl. 2015 Mar;48:700-3. (PMID: 25579973)
Drug Chem Toxicol. 2025 Mar;48(2):367-380. (PMID: 39434256)
Front Oncol. 2020 Jun 24;10:1015. (PMID: 32670884)
Cancers (Basel). 2023 Sep 01;15(17):. (PMID: 37686652)
Cancers (Basel). 2020 Feb 16;12(2):. (PMID: 32079108)
Colloids Surf B Biointerfaces. 2021 Apr;200:111609. (PMID: 33588242)
J Exp Clin Cancer Res. 2019 Jun 20;38(1):270. (PMID: 31221203)
Biochem Biophys Rep. 2021 Mar 14;26:100962. (PMID: 33763604)
Biosensors (Basel). 2022 Sep 04;12(9):. (PMID: 36140107)
ACS Nano. 2012 Mar 27;6(3):2150-6. (PMID: 22303822)
Colloids Surf B Biointerfaces. 2023 Oct;230:113507. (PMID: 37562122)
Sci Rep. 2019 Sep 30;9(1):14004. (PMID: 31570739)
Inorg Chem. 2016 Oct 17;55(20):10267-10277. (PMID: 27667449)
Med Phys. 2020 Mar;47(3):1139-1150. (PMID: 31885094)
Expert Opin Drug Discov. 2025 Oct;20(10):1327-1343. (PMID: 40884784)
J Nanobiotechnology. 2024 Apr 26;22(1):210. (PMID: 38671474)
J Neurosurg. 2023 Feb 10;139(3):748-759. (PMID: 36790010)
Nanoscale. 2019 Nov 28;11(46):22387-22397. (PMID: 31730144)
Adv Mater. 2017 Mar;29(11):. (PMID: 28026064)
Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4009-14. (PMID: 23412337)
ACS Appl Mater Interfaces. 2018 May 23;10(20):17107-17116. (PMID: 29701456)
Nat Commun. 2024 Mar 29;15(1):2724. (PMID: 38553435)
Acc Chem Res. 2013 Mar 19;46(3):662-71. (PMID: 22853558)
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2024 Jul-Aug;16(4):e1976. (PMID: 39091260)
Contrast Media Mol Imaging. 2017 Nov 13;2017:3896107. (PMID: 29259535)
Sci Rep. 2015 Oct 28;5:15675. (PMID: 26507179)
Toxicol Pathol. 2008 Jan;36(1):112-6. (PMID: 18337229)
Bioconjug Chem. 2021 Aug 18;32(8):1455-1471. (PMID: 34319077)
Front Drug Deliv. 2023;3:. (PMID: 37583474)
Trends Cancer. 2020 May;6(5):380-391. (PMID: 32348734)
Science. 2002 Nov 29;298(5599):1759-62. (PMID: 12459582)
Anal Chem. 2021 Jan 19;93(2):777-783. (PMID: 33300344)
Int J Mol Sci. 2022 Sep 15;23(18):. (PMID: 36142693)
ACS Nano. 2018 May 22;12(5):4469-4477. (PMID: 29608274)
Biomaterials. 2011 Nov;32(32):8261-70. (PMID: 21803417)
Adv Colloid Interface Sci. 2020 Nov;285:102274. (PMID: 32992078)
NanoImpact. 2021 Apr;22:100318. (PMID: 35559975)
Acta Neurochir Suppl. 2017;124:303-308. (PMID: 28120088)
Chem Commun (Camb). 2010 Sep 7;46(33):6126-8. (PMID: 20664878)
Cancers (Basel). 2024 Oct 26;16(21):. (PMID: 39518054)
Int J Nanomedicine. 2022 May 02;17:1951-1970. (PMID: 35530976)
ACS Nano. 2015 Nov 24;9(11):11455-61. (PMID: 26458137)
ACS Appl Mater Interfaces. 2024 Mar 20;16(11):13543-13562. (PMID: 38452225)
Int J Biol Macromol. 2022 Jun 15;210:530-544. (PMID: 35513094)
Int J Mol Sci. 2024 Jan 15;25(2):. (PMID: 38256120)
ACS Appl Mater Interfaces. 2020 Jan 22;12(3):3961-3968. (PMID: 31876144)
J Mater Chem B. 2022 Jun 15;10(23):4473-4478. (PMID: 35612558)
Angew Chem Int Ed Engl. 2018 Apr 16;57(17):4652-4656. (PMID: 29479792)
Front Bioeng Biotechnol. 2022 May 27;10:831379. (PMID: 35694230)
J Dairy Sci. 2022 Apr;105(4):2895-2907. (PMID: 35181133)
Int J Mol Sci. 2023 Sep 19;24(18):. (PMID: 37762559)
Colloids Surf B Biointerfaces. 2015 Dec 1;136:989-96. (PMID: 26562191)
Cureus. 2020 May 19;12(5):e8195. (PMID: 32572354)
Nanomaterials (Basel). 2019 Feb 11;9(2):. (PMID: 30754695)
Theranostics. 2019 Feb 12;9(5):1264-1279. (PMID: 30867829)
Int J Mol Sci. 2023 Feb 15;24(4):. (PMID: 36835310)
Nat Rev Immunol. 2019 Aug;19(8):477-489. (PMID: 31036962)
Int J Nanomedicine. 2017 May 22;12:3899-3911. (PMID: 28579776)
Comput Methods Programs Biomed. 2023 Feb;229:107255. (PMID: 36462426)
Sci Adv. 2025 Aug 8;11(32):eadv3316. (PMID: 40779623)
J Colloid Interface Sci. 2023 Nov 15;650(Pt B):1619-1637. (PMID: 37494859)
Front Immunol. 2021 Nov 25;12:790674. (PMID: 34899760)
Sci Rep. 2021 Jul 26;11(1):15196. (PMID: 34312404)
Apoptosis. 2021 Dec;26(11-12):574-599. (PMID: 34687375)
Sci Rep. 2021 Jul 26;11(1):15219. (PMID: 34312463)
Nat Commun. 2018 Jun 20;9(1):2415. (PMID: 29925838)
ACS Appl Mater Interfaces. 2022 Jun 22;14(24):28097-28104. (PMID: 35686447)
Front Oncol. 2021 Oct 22;11:749970. (PMID: 34745974)
Nat Nanotechnol. 2021 Mar;16(3):266-276. (PMID: 33712737)
Photodiagnosis Photodyn Ther. 2023 Jun;42:103566. (PMID: 37059163)
Int J Mol Sci. 2021 Sep 18;22(18):. (PMID: 34576279)
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2276663. (PMID: 37955285)
Langmuir. 2025 Jan 28;41(3):1694-1702. (PMID: 39797801)
Sci Rep. 2025 Jul 14;15(1):25387. (PMID: 40659725)
ACS Nano. 2013 Aug 27;7(8):6858-67. (PMID: 23829293)
Nat Commun. 2021 Nov 25;12(1):6856. (PMID: 34824216)
ACS Appl Bio Mater. 2019 Apr 15;2(4):1432-1439. (PMID: 35026918)
Int J Mol Sci. 2019 Mar 28;20(7):. (PMID: 30925722)
Pharmaceutics. 2024 Aug 13;16(8):. (PMID: 39204409)
Microsyst Nanoeng. 2023 Nov 17;9:145. (PMID: 38025887)
Cell Death Discov. 2024 Nov 11;10(1):466. (PMID: 39528439)
Int J Nanomedicine. 2020 Mar 20;15:1951-1965. (PMID: 32256071)
J Mater Chem B. 2018 May 28;6(20):3366-3371. (PMID: 32254394)
Front Med (Lausanne). 2025 Mar 05;12:1544393. (PMID: 40109724)
Nat Med. 2019 Jan;25(1):44-56. (PMID: 30617339)
Sci Rep. 2024 Feb 12;14(1):3463. (PMID: 38342924)
J Nanobiotechnology. 2021 Apr 1;19(1):96. (PMID: 33794908)
Cancers (Basel). 2024 Jul 24;16(15):. (PMID: 39123366)
Int J Mol Sci. 2023 Nov 29;24(23):. (PMID: 38069213)
Sci Technol Adv Mater. 2025 Feb 6;26(1):2463317. (PMID: 40065760)
Membranes (Basel). 2020 Aug 03;10(8):. (PMID: 32756454)
Mater Sci Eng C Mater Biol Appl. 2020 Mar;108:110376. (PMID: 31924027)
Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):143-158. (PMID: 32207347)
NanoImpact. 2025 Jul;39:100572. (PMID: 40527434)
Mater Sci Eng C Mater Biol Appl. 2017 Feb 1;71:412-424. (PMID: 27987725)
ACS Appl Mater Interfaces. 2021 Sep 15;13(36):42357-42369. (PMID: 34472848)
ACS Biomater Sci Eng. 2023 Jan 9;9(1):449-457. (PMID: 36475590)
Nat Commun. 2024 Mar 21;15(1):2530. (PMID: 38514624)
ACS Nano. 2020 Oct 27;14(10):13304-13315. (PMID: 33016066)
J Mater Chem B. 2020 Dec 7;8(45):10290-10308. (PMID: 33103712)
Sci Rep. 2022 Jan 7;12(1):164. (PMID: 34997074)
Colloids Surf B Biointerfaces. 2025 May;249:114520. (PMID: 39823950)
Nanomaterials (Basel). 2023 Sep 15;13(18):. (PMID: 37764594)
Bioconjug Chem. 2024 Jun 19;35(6):715-731. (PMID: 38775705)
Biomaterials. 2009 Jan;30(1):19-25. (PMID: 18848354)
Heliyon. 2023 Apr 10;9(4):e15150. (PMID: 37095995)
Sensors (Basel). 2011;11(12):11036-55. (PMID: 22247651)
Med Res Rev. 2023 Jul;43(4):717-774. (PMID: 36757198)
ACS Nano. 2020 Jul 28;14(7):8343-8358. (PMID: 32525656)
Int J Mol Sci. 2021 Apr 27;22(9):. (PMID: 33925347)
Adv Drug Deliv Rev. 2008 Aug 17;60(11):1226-1240. (PMID: 18495291)
Anal Biochem. 2007 May 15;364(2):193-203. (PMID: 17368555)
J Nanosci Nanotechnol. 2014 Jul;14(7):5355-62. (PMID: 24758031)
J Clin Oncol. 2008 May 1;26(13):2192-7. (PMID: 18445844)
ACS Nano. 2024 Aug 27;18(34):23090-23103. (PMID: 39143650)
Pharmacol Rev. 2018 Jul;70(3):412-445. (PMID: 29669750)
Neurooncol Adv. 2022 Jun 21;4(1):vdac097. (PMID: 35911637)
MedComm (2020). 2024 Jun 22;5(7):e603. (PMID: 38911063)
ACS Sens. 2023 Dec 22;8(12):4686-4695. (PMID: 37983019)
ACS Nano. 2015 Jan 27;9(1):488-95. (PMID: 25549258)
Nat Mater. 2005 Jun;4(6):435-46. (PMID: 15928695)
ACS Appl Mater Interfaces. 2023 Apr 19;15(15):18672-18684. (PMID: 37018127)
Int J Mol Sci. 2022 Jun 02;23(11):. (PMID: 35682929)

Keywords: artificial intelligence (AI); bioconjugated quantum dots (QDs); click chemistry; glioblastoma (GB); photodynamic therapy (PDT); precision imaging

Date Created: 20260128 Date Completed: 20260128 Latest Revision: 20260131

20260131

PMC12839401

10.3390/cells15020185

41597259