Sortilin-Targeted Peptide Conjugates for MDR Cancer Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Cancer treatment is hindered by multidrug resistance (MDR) and tumour heterogeneity, which complicates the effectiveness of chemotherapy and targeted therapeutics, leading to limited clinical progress and variable treatment responses.
Innovation Solution
Development of peptide compounds and conjugate compounds that target sortilin receptor on cancer cells, enhancing drug delivery and overcoming MDR by forming conjugates with therapeutic agents, such as anticancer drugs or phytochemicals, and using them in drug delivery systems like liposomes or nanoparticles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional chemotherapy is used to treat cancer, then cancer cells may be killed, but multidrug resistance (MDR) develops causing treatment failure
Solution Approach 1:
The patent uses sortilin receptor as an intermediary target to deliver chemotherapy drugs specifically to cancer cells. The peptide compounds bind to sortilin receptors on the cancer cell surface, facilitating targeted drug delivery and bypassing the P-gp efflux pump mechanism that causes MDR. This mediator approach allows drugs to enter cells through receptor-mediated endocytosis rather than passive diffusion, overcoming resistance mechanisms.
2Object-affected harmful factors
If P-glycoprotein (P-gp) pumps out anticancer drugs, then cancer cells survive, but drug uptake is blocked preventing cytotoxic concentrations
Solution Approach 1:
The sortilin receptor serves as an intermediary entry mechanism that bypasses P-gp efflux. The peptide-drug conjugates are internalized through sortilin-mediated endocytosis, delivering drugs directly into the cell interior where they can accumulate to cytotoxic concentrations without being pumped out by P-gp at the plasma membrane.
Solution Approach 2:
The patent replaces passive diffusion and active transport mechanisms (which are subject to P-gp efflux) with receptor-mediated endocytosis. This substitution of the drug entry mechanism allows bypassing the mechanical efflux pump system, enabling drug accumulation inside MDR cells.
3Adaptability or versatility
If tumour heterogeneity is present, then cancer cells show genetic diversity, but treatment response becomes variable and unpredictable
Solution Approach 1:
The patent targets sortilin receptor which appears to be universally expressed across different cancer cell types and genetic backgrounds. By using a universal target (sortilin) rather than targeting specific genetic mutations, the therapy can effectively treat heterogeneous tumours with diverse genetic profiles, providing consistent treatment response across variable cancer populations.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The peptide-conjugate compounds enhance drug uptake in cancer cells, inducing apoptosis and reducing migration, while maintaining tolerability, thus providing a more effective cancer treatment approach.
Implementation Method 1
peptide compounds and conjugate compounds that target sortilin receptor on cancer cells, enhancing drug delivery
Implementation Method 2
The peptide-conjugate compounds enhance drug uptake in cancer cells, inducing apoptosis
Data Source
AI summary
The present disclosure relates to peptide compounds and conjugate compounds, processes, methods and uses thereof for treating cancer. For example, the compounds can comprise compounds of formula(I)(SEQ ID NO: 1)X1X2X3X4X5GVX6AKAGVX7NX8FKSESY(II)(SEQ ID NO: 2)(X9)nGVX10AKAGVX11NX12FKSESY(III)(SEQ ID NO: 3)YKX13LRRX14APRWDX15PLRDPALRX16X17L(IV)(SEQ ID NO: 4)YKX18LRR(X19)nPLRDPALRX20X21L(V)(SEQ ID NO: 5)IKLSGGVQAKAGVINMDKSESM(VI)(SEQ ID NO: 6)IKLSGGVQAKAGVINMFKSESY(VII)(SEQ ID NO: 7)IKLSGGVQAKAGVINMFKSESYK(VIII)(SEQ ID NO: 8)GVQAKAGVINMFKSESY(IX)(SEQ ID NO: 9)GVRAKAGVRNMFKSESY(X)(SEQ ID NO: 10)GVRAKAGVRN(Nle)FKSESY(XI)(SEQ ID NO: 11)YKSLRRKAPRWDAPLRDPALRQLL(XII)(SEQ ID NO: 12)YKSLRRKAPRWDAYLRDPALRQLL(XIII)(SEQ ID NO: 13)YKSLRRKAPRWDAYLRDPALRPLLwherein X1 to X21 and n can have various different valuesand wherein at least one protecting group and/or at least one labelling agent is optionally connected to said peptide compound at an N- and/or C-terminal end.