NIR Dye Conjugates Sensitize Cancer Cells to Cisplatin
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Solution Overview
Problem
Current cancer therapies, particularly those for aggressive and metastatic cancers, often face challenges with drug resistance, leading to limited treatment options and severe side effects.
Innovation Solution
The development of DZ-DRG amide or ester conjugates, which are NIR dye conjugates linked to resistance-prone therapeutics (RPTs) such as Cisplatin, Simvastatin, or Artemisinin, to sensitize cancer cells and overcome therapeutic resistance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If resistance-prone therapeutics (RPTs) such as Cisplatin are used to treat aggressive and metastatic cancers, then therapeutic effect is achieved, but drug resistance develops leading to treatment failure
Solution Approach 1:
The patent introduces NIR dye conjugates as intermediary substances that mediate between the RPT and the cancer cells. These conjugates include the RPT molecule linked to a NIR dye through amide or ester bonds, allowing the NIR dye to act as a carrier and sensitizer that enhances RPT delivery and effectiveness while overcoming resistance mechanisms
Solution Approach 2:
The patent creates composite therapeutic agents by chemically conjugating NIR dyes with RPTs. This composite structure combines the cytotoxic properties of the RPT with the tumor-targeting and sensitizing capabilities of the NIR dye, resulting in a molecule that overcomes drug resistance while maintaining therapeutic efficacy
2Reliability
If higher doses of RPTs are administered to overcome drug resistance, then therapeutic response may be improved, but side effects increase
Solution Approach 1:
The NIR dye conjugates exhibit local quality by preferentially accumulating in tumor tissues through enhanced permeability and retention (EPR) effects and active targeting mechanisms. This localized concentration allows high therapeutic doses to be delivered specifically to cancer cells while minimizing exposure and side effects in healthy tissues
Solution Approach 2:
The NIR dye acts as an intermediary that facilitates selective delivery of the RPT to tumor cells. The conjugate structure allows the NIR dye to guide the RPT to the target site, enabling effective dosing without the systemic toxicity associated with high doses of unconjugated RPTs
3Productivity
If conventional cancer therapies are used, then initial treatment effect is achieved, but resistance develops limiting further treatment options
Solution Approach 1:
The NIR dye conjugates possess multiple functions: they serve as the therapeutic agent (RPT), as a tumor-targeting vehicle, as a resistance-overcoming sensitizer, and potentially as an imaging probe. This multi-functionality allows a single conjugate to address multiple aspects of cancer therapy, maintaining treatment efficacy and expanding therapeutic options
Solution Approach 2:
The patent changes key parameters of the therapeutic approach by modifying the chemical structure of the RPT through conjugation with NIR dyes. This structural modification alters the pharmacokinetic and pharmacodynamic properties, including cellular uptake, distribution, and sensitivity profiles, thereby overcoming resistance and maintaining treatment versatility
Data Source
AI summary
The present invention generally relates to sensitizer compounds and their use to sensitize cancer and/or pre-cancerous cells of certain cancers to treatment with certain resistance-prone therapeutics used in cancer therapy. In embodiments, the conjugates of particular esters or amides of Near Infrared Dyes, are used as sensitizers to avoid or overcome therapeutic resistance once formed. In embodiments, the sensitizers include conjugates with Cisplatin, Simvastatin, Artemisinin, platin-based compounds or statins. In embodiments, the resistance prone cancer therapeutics include cisplatin, gemcitabine, doxorubicin, paclitaxel, docetaxel, and platin-based compounds. These may be administered in combination with the sensitizer, or the sensitizer itself may comprise an therapeutci-derived moiety conjugated to the sensitizer, for example as is the case for dye-CIS conjugated sensitizers. Alternatively, the sensitizer may be co-administered with one or more therapeutic. Embodiments of the invention may advantageously be used in cancers that have a tendency to develop resistance to such cancer therapeutics and/or to form metastases, including e.g. lung, pancreatic, prostate, testicular, ovarian, cervical, bladder, breast, head and neck, esophageal, and stomach, cancers, germ cell tumors, lymphomas and other cancers.