Say no to drugs: Bioactive macromolecular therapeutics without conventional drugs

Rütter, Marie; Milošević, Nenad; David, Ayelet

doi:10.1016/j.jconrel.2020.11.026

Cited by 11 publications

(12 citation statements)

References 167 publications

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“…The controlled self‐assembly of synthetic and biological macromolecules into the advanced hybrid materials is enabled by the biorecognition of biological motifs, i.e., receptors, antigens, binding sites, and targeting ligands, such as proteins, peptides, antibody fragments, nucleic acid aptamers, and carbohydrates. [ 17–21 ] Even though high‐affinity ligands mediate biological signaling pathways, these small molecules alone are not able to reach their respective target sites due to their limited stability besides their short half‐life in the circulation. [ 21 ] Here, tailored nanomedicine design is opening a new paradigm in the application of macromolecules in medicine.…”

Section: Concept Of “Drug‐free” Macromolecular Therapeuticsmentioning

confidence: 99%

“…[ 17–21 ] Even though high‐affinity ligands mediate biological signaling pathways, these small molecules alone are not able to reach their respective target sites due to their limited stability besides their short half‐life in the circulation. [ 21 ] Here, tailored nanomedicine design is opening a new paradigm in the application of macromolecules in medicine. The used biomimetic strategies provide the possibility of influencing specific tissue or cellular activities.…”

Section: Concept Of “Drug‐free” Macromolecular Therapeuticsmentioning

confidence: 99%

“…These systems are able to increase the binding affinity to several orders of magnitude over the free ligand. [ 21 ]…”

Section: Concept Of “Drug‐free” Macromolecular Therapeuticsmentioning

confidence: 99%

“…Thus far, several therapeutic systems using the DFMT approach that do not carry a low‐molecular‐weight drug and whose therapeutic activity is mediated by biorecognition, were designed and described. [ 21,30 ] We are aware that any compound with a pharmacological effect is considered a drug in the regulatory sense, however this review considers the term of DFMT proposed by Kopecek. The DFMT systems reviewed in this paper include hybrid copolymers consisting of synthetic and natural macromolecules crosslinking the receptors at the surface of blood cancer cells, [ 31–33 ] macromolecules‐employed targeting E‐selectin receptors in the vasculature, [ 34,35 ] glycopolymers for the depletion of Gal‐3, [ 24,36 ] or systems for the targeted biomineralization of the cancer cells driven by the receptor–ligand recognition.…”

Section: Concept Of “Drug‐free” Macromolecular Therapeuticsmentioning

confidence: 99%

See 3 more Smart Citations

Polymer‐Based Drug‐Free Therapeutics for Anticancer, Anti‐Inflammatory, and Antibacterial Treatment

Tavares

Pechar

Chytil

et al. 2021

Macromolecular Bioscience

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This paper summarizes the area of biomedicinal polymers, which serve as nanomedicines even though they do not contain any anticancer or antiinflammatory drugs. These polymer nanomedicines with unique design are in the literature highlighted as a novel class of therapeutics called “drug‐free macromolecular therapeutics.” Their therapeutic efficacy is based on the tailored multiple presentations of biologically active vectors, i.e., peptides, oligopeptides, or oligosaccharides. Thus, they enable, for example, to directly induce the apoptosis of malignant cells by the crosslinking of surface slowly internalizing receptors, or to deplete the efficacy of tumor‐associated proteins. The precise biorecognition of natural binding motifs by multiple vectors on the polymer construct remains the crucial part in the designing of these drug‐free nanomedicines. Here, the rationales, designs, synthetic approaches, and therapeutic potential of drug‐free macromolecular therapeutics consisting of various active vectors are described in detail. Recent developments and achievements for namely B‐cell lymphoma treatment, Gal‐3‐positive tumors, inflammative liver injury, and bacterial treatment are reviewed and highlighted. Finally, a possible future prospect within this highly exciting new field of nanomedicine research is presented.

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Section: Concept Of “Drug‐free” Macromolecular Therapeuticsmentioning

confidence: 99%

Section: Concept Of “Drug‐free” Macromolecular Therapeuticsmentioning

confidence: 99%

“…These systems are able to increase the binding affinity to several orders of magnitude over the free ligand. [ 21 ]…”

Section: Concept Of “Drug‐free” Macromolecular Therapeuticsmentioning

confidence: 99%

Section: Concept Of “Drug‐free” Macromolecular Therapeuticsmentioning

confidence: 99%

See 2 more Smart Citations

Polymer‐Based Drug‐Free Therapeutics for Anticancer, Anti‐Inflammatory, and Antibacterial Treatment

Tavares

Pechar

Chytil

et al. 2021

Macromolecular Bioscience

View full text Add to dashboard Cite

show abstract

“…Drug-free macromolecular therapeutics (DFMT) is a new paradigm for the treatment of malignancies [ 11 , 12 , 13 ]. Induction of apoptosis is mediated by receptor crosslinking facilitated by biorecognition of complementary peptide or oligonucleotide motifs; no low molecular weight drug is needed [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Crosslinking of CD38 Receptors Triggers Apoptosis of Malignant B Cells

Gambles

Wang

et al. 2021

Molecules

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Recently, we designed an inventive paradigm in nanomedicine—drug-free macromolecular therapeutics (DFMT). The ability of DFMT to induce apoptosis is based on biorecognition at cell surface, and crosslinking of receptors without the participation of low molecular weight drugs. The system is composed of two nanoconjugates: a bispecific engager, antibody or Fab’ fragment—morpholino oligonucleotide (MORF1) conjugate; the second nanoconjugate is a multivalent effector, human serum albumin (HSA) decorated with multiple copies of complementary MORF2. Here, we intend to demonstrate that DFMT is a platform that will be effective on other receptors than previously validated CD20. We appraised the impact of daratumumab (DARA)- and isatuximab (ISA)-based DFMT to crosslink CD38 receptors on CD38+ lymphoma (Raji, Daudi) and multiple myeloma cells (RPMI 8226, ANBL-6). The biological properties of DFMTs were determined by flow cytometry, confocal fluorescence microscopy, reactive oxygen species determination, lysosomal enlargement, homotypic cell adhesion, and the hybridization of nanoconjugates. The data revealed that the level of apoptosis induction correlated with CD38 expression, the nanoconjugates meet at the cell surface, mitochondrial signaling pathway is strongly involved, insertion of a flexible spacer in the structure of the macromolecular effector enhances apoptosis, and simultaneous crosslinking of CD38 and CD20 receptors increases apoptosis.

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Hemoglobin Nanocrystals for Drugs Free, Synergistic Theranostics of Colon Tumor

Zhou

et al. 2022

Small

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The conventional approach in cancer nanomedicine involves advanced drug nanocarriers delivering preloaded therapeutics to targeted tumor sites to maximize drug efficiency. However, both cancer drugs and nanocarriers inevitably produce side effects and systemic toxicity. Herein, hemoglobin nanocrystals (HbC) as drug‐free theranostic nanoformulations with the tumor microenvironment (TME) activated diagnostic and therapeutic abilities towards colon tumors are introduced. HbC can release Fe2+ oxidized to Fe3+ in the Fenton reaction with tumor endogenous H2O2, concurrently with the generation of cytotoxic hydroxyl radicals (•OH) that allow for chemodynamic therapy (CDT). Furthermore, in situ‐produced Fe3+ reacts with colon tumor‐abundant H2S, resulting in the production of Fe1−xS, which provides magnetic resonance imaging (MRI) contrast and allows for NIR light‐inducible photothermal therapy (PTT). In vitro and in vivo studies revealed that HbC produced CDT towards 4T1 tumors, and MRI‐guided, synergistically enhanced combination of CDT and PTT against H2S abundant colon tumors (CT26), with negligible toxicity towards normal tissues, enlightening HbC as highly efficient and biocompatible TME activated theranostic nanoplatform specific against colon cancer without any traditional drugs and drug carriers.

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Say no to drugs: Bioactive macromolecular therapeutics without conventional drugs

Cited by 11 publications

References 167 publications

Polymer‐Based Drug‐Free Therapeutics for Anticancer, Anti‐Inflammatory, and Antibacterial Treatment

Polymer‐Based Drug‐Free Therapeutics for Anticancer, Anti‐Inflammatory, and Antibacterial Treatment

Crosslinking of CD38 Receptors Triggers Apoptosis of Malignant B Cells

Hemoglobin Nanocrystals for Drugs Free, Synergistic Theranostics of Colon Tumor

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