The present invention relates to a targeted protease degradation (TED) platform, and specifically to a conjugate of target molecule-linker-E3 ligase ligand as shown in formula I, R.sub.T-L1-R.sub.E3 (formula I), wherein R.sub.T is a monovalent group of the target molecule, R.sub.E3 is a monovalent group of the E3 ligase ligand, L1 is the linker linking A and B, and L1 is as shown in formula II below: —W-L2-W.sup.2— (II).

The invention provides a long-acting parathyroid hormone peptide (PTH) that is retained in a subject's blood serum for periods of time that greatly exceed the natural hormone. The long-acting PTH is conjugated to at the carbon 3 position of a non-hormonal vitamin D via a scaffold of discreet length that facilitates its purification, detection, solubility, and efficacy at the PTH receptor (PTHR). The PTH may be conjugated to the non-hormonal vitamin D via a 36 mer poly(ethylene glycol) moiety (PTH-PEG36-VitD). The invention also provides optimized manufacturing methods and formulations. The PTH-PEG36-VitD has a vastly-improved serum half-life and bioavailability when compared to a non-conjugated PTH peptide. PTH-PEG36-VitD also significantly increases serum calcium, reduces urinary calcium, and reduces serum phosphate.

The invention provides non-hormonal Vitamin D conjugated to G-CSF or compounds with G-CSF activity or GM-CSF or compounds having GM-CSF activity singly or in combination that result in increased absorption, bioavailability or circulating half-life when compared to non-conjugated forms.

The present invention discloses a drug delivery system for targeted therapy comprising a functionalized lipid-based nanoplatform, where at least one ligand is coupled to the surface of the nanoplatform and encapsulates at least one pharmaceutically active ingredient. A process for obtaining the drug delivery system of the present invention is also disclosed as well as a composition comprising the system of the invention. The invention relates to the field of medicine and biotechnology. The present solution aims at developing targeting co-encapsulating nanostructured lipid carriers for the treatment of different types of cancer, including glioblastoma, as well as other diseases and disorders, envisioning the establishment of an in vitro/in vivo correlation.

Nanoparticles and formulations for treating prostate cancer in a subject are disclosed. The nanoparticles contain a cage, such as a zeolitic imidazolate framework (“ZIF”), a surface modifying agent, a targeting ligand, and an active agent. The surface modifying ligand is attached to the outer surface of the cage and the targeting ligand is exposed to the surrounding environment. The active agent is encapsulated in the cage. The targeting ligand binds to a reproductive hormone or a receptor of a reproductive hormone. The active agents can be a ribosome inactivating protein, an apoptosis inducer, a hormone, a receptor ligand, or a nucleic acid, or a chemotherapy drug or a combination thereof, that kill and/or reduce or prevent growth or proliferation of gonadotroph cells and/or tumor cells, regulate FSH and/or LH secretion, and/or interfere with androgen production. Uses for formulations incorporating the nanoparticles for treating cancer in a subject are also disclosed.

Provided herein are methods and compositions for the delivery of a combination of oxiplatin and folinic acid to a cell, tissue, or physiological site. The compositions comprise delivery system complexes comprising liposomes encapsulating dihydrate(1,2-diaminocyclohexane)platinum(II)-folinic acid or delivery system complexes comprising a 5-fluorouracil active metabolite. Also provided herein are methods for the treatment of cancer, wherein the methods comprise administering the delivery system complexes comprising dihydrate(1,2-diaminocyclohexane)platinum(II)-folinic acid or delivery system complexes comprising a 5-fluorouracil active metabolite that have therapeutic activity against the cancer.

A novel anti-tumor agent capable of delivering siRNA or shRNA specifically to pancreatic cancer cells and suppressing tumor growth, invasion, and metastasis of pancreatic cancer is provided. The present invention provides a nucleic acid delivery enhancer for delivering siRNA or shRNA into cells, which consists of a folic acid-cationic oligopeptide complex. The present invention also provides an anti-tumor agent having siRNA or shRNA capable of binding to mRNA or snoRNA expressed in pancreatic cancer cells to inhibit its expression and a folic acid-cationic oligopeptide complex. The siRNA is capable of binding to RNA selected from the group consisting of, for example, SNORA18 snoRNA, NUP85 mRNA, WASF2 mRNA, and SNORA22 snoRNA.

The disclosure relates to nanoparticle drug conjugates (NDC) that comprise ultrasmall nanoparticles, folate receptor (FR) targeting ligands, and linker-drug conjugates, and methods of making and using them to treat cancer.

Dry powder formulations for pulmonary and/or intranasal drug delivery, delivery systems, and methods of making and using thereof have been developed. The dry powder formulation contains particles containing a retinoid and/or a retinoid derivative, such as tamibarotene; and a β-cyclodextrin and/or a β-cyclodextrin derivative. The dry powder formulation allows for improved drug adsorption and bioavailability in vivo. The particles of the dry powder formulation have favorable aerodynamic properties for deposition and retention in the lower and/or upper respiratory tract(s). The dry powder formulation can be prepared using spray-drying or spray-freeze-drying. Inhalation, intratracheal administration, and/or intranasal administration of the dry powder formulation can deliver to a subject an effective amount of the retinoid and/or retinoid derivative to prevent, treat, or ameliorate symptom(s) associated with a respiratory viral infection in the subject.

A photosensitizer and derivative, application thereof. The photosensitizer has the structure of general formula I, wherein X is S or Se, Y is organic or inorganic ion, R.sub.1 and R.sub.2 are independently selected from H, alkyl, alkoxy, alkyl amido, alkyl azide and the like; R.sub.3 is selected from H, alkyl, alkoxy, amino sulfonyl, hydroxyl, carboxyl and the like, and L.sub.1 is a linker selected from —(CH.sub.2).sub.n1— or —(CH.sub.2CH.sub.2O).sub.n2—. The derivatives are molecular medicines with drug molecules of anticancer and chemotherapy or tumor targeting function connected to the said photosensitizer. The photosensitizer has excellent near infrared characteristics and low dark toxicity and is used in the field of photodynamic tumor therapy. The introduction of benzophenothiazine or benzophenoselenazine into derivatives with tumor-targeting function could improve the specific uptake of photosensitizer in tumor tissues. Moreover, clinical anticancer drugs can be introduced into the structure of benzophenothiazine or benzophenoselenazine to achieve the purpose of combining therapy of photodynamic therapy and chemotherapy. ##STR00001##