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Designing micelles and targeted protein platforms for near-infrared imaging and photothermal therapy of tumors Nicole Alejandra Carrillo-Malani

Dissertations & Theses @ University of Pennsylvania Available online

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Format:
Book
Thesis/Dissertation
Author/Creator:
Carrillo-Malani, Nicole Alejandra, author.
Contributor:
University of Pennsylvania. Pharmacology., degree granting institution.
Language:
English
Subjects (All):
Bioengineering.
Biomedical engineering.
Oncology.
Medical imaging.
0202.
0574.
0541.
0992.
Local Subjects:
Bioengineering.
Biomedical engineering.
Oncology.
Medical imaging.
0202.
0574.
0541.
0992.
Genre:
Academic theses
Physical Description:
1 online resource (185 pages)
Contained In:
Dissertations Abstracts International 87-12B
Place of Publication:
Ann Arbor : ProQuest Dissertations and Theses, 2026
Language Note:
English
Summary:
Solid tumors remain difficult to treat because complete surgical resection is often limited by poor intraoperative visualization, while chemotherapy and radiation therapy can cause significant off-target toxicity. Photothermal therapy (PTT) offers a minimally invasive alternative in which light-absorbing agents convert near-infrared (NIR) light into localized heat, and its utility can be further enhanced by pairing treatment with imaging for real-time tumor detection and treatment guidance. In this dissertation, I developed and evaluated two complementary theranostic platforms for NIR imaging and PTT of tumors: polymeric micelles loaded with phthalocyanine or naphthalocyanine dyes, and a targeted helical protein scaffold engineered for high-density dye conjugation. In Chapter 2, I synthesized a panel of metal-chelated phthalocyanine and naphthalocyanine derivatives, formulated them into PEG-PCL micelles, and compared their physiochemical properties, photoacoustic imaging performance, and photothermal efficacy under 810 nm and 980 nm irradiation. These studies identified CuNc(Octa) and SnNc(Octa) as optimal micelle formulations for NIR-I and NIR-II applications, respectively, and showed that although 980 nm irradiation enabled deeper tissue penetration and strong in vivo treatment efficacy, it also produced more rapid healthy tissue heating at the maximum permissible exposure. In Chapter 3, I designed a modular eight-helix protein scaffold bearing 20 surface-exposed cysteine residues to enable dense, site-specific conjugation of AQuora800-maleimide. Screening multiple HER2-targeting ligand variants identified the affibody dimer construct AD-20AQ as the lead candidate, with strong binding, cellular uptake, prolonged circulation, and preferential tumor accumulation compared to AD-1AQ. AD-20AQ achieved complete tumor ablation after a single intravenous dose followed by 810 nm laser irradiation, with no observed recurrence. Together, these studies demonstrate that both micellar and protein-based platforms can be engineered to improve optical performance, tumor targeting, and therapeutic efficacy in NIR-guided PTT. More broadly, this work establishes adaptable design strategies for theranostic agents that can be tuned for different wavelengths, imaging modalities, and cancer targets
Notes:
Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
Advisors: Tsourkas, Andrew; Delikatny, Edward J. Committee members: Farwell, Michael; Brenner, Jacob
Ph.D. University of Pennsylvania 2026
Vendor supplied data
Local Notes:
School code: 0175
ISBN:
9798247973454
Access Restriction:
Restricted for use by site license

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