US8530429 B2 US20140286872 A1 WO2010124004 A2 US20150118311 A1 Patent No. targeting Nanoparticle Invasive Treating Therapy Nanocarrier CNS treatment nanocarriers penetrative Highly methods peptides targeting Brain benzylguanine delivery tumors

disease Title

Tumors

of

tumor

brain

and and

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Inc. Therapeutics, Arch ation Commercializ Center Through Washington University University Yale  

Technology Institute Georgia University Emory Owner

Cancer

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Senger, Rahn, S.M. Robbins, Veiseh, Stephen, Silber, Kievit, R.G. Ellenbogen, Zhang, Arbiser, , Bellamkonda J.M. Munson, W.M. Saltzman, J.M. Piepmeier, Patel, Zhou,

R.V. Inventor

T.R.

Z. J. F. J.R.

M.

O.

J.L. D.L.

Z.

agent radioactive agent Anti benzylguanine O6 Imipramine agents detectable or magnetic, radioactive, - camptothecin. Paclitaxel, Temozolomide (BCNU), Carmustine iodide Dithiazanine -

Diagnosis Treatment

ultrasound - - tumor

APIs

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formulated appropriately vesicle PEGylated salt pharmaceutically Imipramine enhanced intracranial and can polymeric S (HIGCs). highly initiating identified subtype to length amino A to material polyethylene Coated blood mall

targeting O6

bind

or be - -

benzylguanine. brain prodrug,

are selected invasive

liposome

Description of

acid includes loaded

preferentially

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nanoparticles

human

to as uni blue, barrier. brain peptide

optimized sized

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in residues brain

for

glioma

- (BTICs) a

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glutathione

GBM (CED).

and

the its of oligomer

s

12 tumor ability drugs

to

cells cells

that

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for consisting 20 or in a

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- sensitive copolymer o co Nanoparticle PEGylated thereof. copolymers, as Ethylcellulose, Hydroxypropyl Polycaprolactone, Poly copolymers hydroxybutyrate Polyglycolide Poly(ester Polyanhydrides, (PLA Poly(lactic Poly(lactic Poly(lactic r

- cetyl gly - well - 4

PEG) colide) - hydroxybutyrate

alcoholipolysorbate of crosslinks

Carrier/Polymer - anhydrides),

acid) co as as

unilamillar

acid) block thereof,

cross - copolymer,

glycolic made

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blends,

and (PLA), -

core copolymers,

(PGA), cellulose, - polyethyleneglycol linked covalently

methylcellulose,

of (PHB)

liposomes acid)

material

combinations

poly(lactide

cyclodextrin derivatives,

(PLGA)

chitosan (P4HB),

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Coat

and -

3

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to (CTX) e.g. nucleic proteins, peptides, molecules, Small targeting Passive (BSCSs) stem brain agents Antitumor   

pep and Angio general: (GBM) Glioblastoma For BTICs. for 11 SEQ HIGCs, targeting is ID peptide Targeting MMP2 Targeting

-

Agent

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used 7

that targeting ID -

to

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BTIC HGIC subtypes Glioblastoma multiform) (Glioblastoma brain TMZ gliomas such Brain (GBM) Glio Type Cancer blastoma -

resistant as

cancers tumors and

of

  expressed (MGMT) methyltransferase O6 O6 normal tumor preferentially permeability) permeability c Liposomes  

apillaries Mechanism diagnosis radionuclide treatment, cancer conjugated The alone. inhibited tumor BTIC Migration brain fluid gradient, positive the Agents delivery Convection - - methylguanine benzylguanine

tissue, tissue. interstitium movement

peptide brain

cells

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relative (enhanced HGIC and toward

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tumors inhibits DNA

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US 20110002846 A1 US8188221 B2 WO2014095916 A1 US20140154269 A1 WO2014138391 A1 tumor target therapeutic Ninjurin brain treatment use vectors Targeted brain metabolism glutamine Targeting of and primarys target therapeutic diagnostic marker tumor CD24 to Peptide

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R.M. Auvergne, Sim, S.A. Goldman, Bergers, Ruoslahti, P. Laakkonen, Mahmudi, Curet, O. Chao, M.A. Sharpe, Baskin, Marcano, Berlin, Tour, Eberhart, Taylor, Ahsan, Hanaford, Raabe,

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Ninjurin Antagonist   and cycle arrests inhibitor, topoisomerase  (DON) norleucine Diazo (Acivicin) yljethanoic oxazol dihydro chloro Amino[(55) inhibitor: metabolism Glutamine

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protein CD24 targeting y Antigen/Antibod peptide CGLSGLGVA via Active antibodies anti (GFAP) acidic  (EGFR) Receptor Growth  13R) receptor  as antigens GBM targeting Passive

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WO2014078522 A1 US 20110178046 A1 US20140039489 A1 WO2012151523 A1 WO2014089209 A2 based electrical disruption brain Acute brain for Csf proteins specific penetrating barrier Blood glioblastoma for methods Materials Glioblastoma Treating Methods

- treatment 1r

tumors

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Research Cancer Institute Kettering Sloan Novartis

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               

Wojton, Kaur, Moser, Gilbert, Ross, Garcia, J. Rossmeisl, V. Davalos, Sutton, Joyce, Daniel, Harris, Goodearl, J. Sterman, Ghayur, D. Hanzatian,

H. S. K.

B. A.

J.

M

R. D. J. C. P.

J.

T.

H. R.

.C. A.

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inhibitors secretase gamma such Notch agents diagnostic antitumor Bioactive salt y pharmaceuticall yl; hydroxycycloalk and carboxamide, alkyl pyrazole in formula inhibitor CSF  polypeptide) atidylserined Dioleoylphosph conjugated related (Saposin 

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Notch synergistically glioblastoma

carrying a

combination combination

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the invention DOPS

domain

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secretase proteins

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a

phospholipid,

incorporating

(DVD)

can

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targeting Passive targeting Passive binding domain A

dual N/A N/A

protein variable

(DVD)

Treatment Treatment or Treatment Treatment treatment and diagnosis P revention,

diagnosis

Glioblastoma (GBM) Glioblastoma glioblastoma particularly Brain glioblastoma particularly Brain Brain

tumors tumors Cancer

charged fusion cross selectively  glioma phosphatidylserine exposed  tumors. expressed stem active  GBM. senescence greatly temozolomide alkylating quiescence agent with inhibitor) gamma Notch  macrophages of inhibit penetrate to 1 Effectiveness a pulsed near volume disruption cause tumor) brain Pulsed vascular expressed comprises bind (DVD) Dual

SapC SapC The The

specified

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inhibitors

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due

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tissue

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inhibitor

cells that electric in DOPS DOPS variable e of Tumor chemotherapeutic to

Binding epithelium lectric

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pa

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effectively BBB fields interval. secretase

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BBB

model activities believed abil receptor

through domain antigen protein targets (TMZ))

of

agent, neural

tissue

CSF over as brain brain ity

of over

in and can into

cell cell

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on as as

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2014 2011 2014 2012 2014

[ [ [ [ [ 14 13 12 11 10 ] ] ] ] ]

(PtdSer).  SapC-DOPS exerts anti- angiogenic effects by inhibiting the growth of blood vessels.

Polymeric The  Wu, X Y. N/A Nanoparticles of the  Polymethacrylic acid grafted starch N/A Treatment Brain Tumors PS80 is capable of

nanoparticles governing  Shalviri, A. invention include a polymer (PMAA-g-St) nanoparticles and binding to Apolipoprotien A1 useful in council of the backbone having grafted to  Polymeric backbone, the monomer diagnosis E (Apo-E), which in turn theranostics. University of polymeric chains containing is methacrylic acid (MAA), binds to LDL receptors in Toronto carboxyl groups or amino brain microvessels, diethylaminoethyl methacrylate 2013 [15] groups, covalently linked as (DEAEM), and the polyethoxy- lated enabling transcytosis of part of the nanoparticle are moieties are provided by polysorbate the nanoparticle. polyethoxylate moieties that 80 (Tween® 80).

WO2013127004 present on the exterior surface of the nanoparticles.

Diagnosis and Welcome  Furness, S. N/A  The invention provides a method for the localization, diagnosis, Active targeting Treatment Brain tumors The compound bind to

A1 treatment of Receptor or diagnosis calcitonin receptor,  Johns, T. prognosis, and/or prediction of therapeutic outcome of a brain brain tumors. Antibodies  Wookey, P. tumor in a subject. allowing the compound to Pty Ltd J.  The method details detecting calcitonin receptor in brain cells of bind to cells within the [16] the subject, wherein the presence of calcitonin receptor localizes, subject, and determining 2012 is diagnostic, prognostic and/or predictive for, the brain tumor. the location of the compound within the brain of the subject or WO2012000062 delivers drug.

Glioblastoma The Regents  Liu, B. N/A The disclosure provides N/A Antibody/antige Treatment Glioblastoma Anti-GMB antibody binds multiforme- Of The  Marks, J. D. isolated antibodies that binds n or diagnosis to the GMB tumor cells, reactive University Of  Zhu, X. specifically to glioblastoma inhibiting proliferation and antibodies and California  Bidlingmaier, multiform (GBM) tumor self-renewal of tumor 2012 [17] A1 methods of use S. sphere cells. initiating cells.

thereof US20120039915

Nanocarrier  Rosetta  Yerushalmi, Nucleic acid A cationic carrier system Cationic carrier system Passive Treatment Brain tumors PG-NH2 accumulates in

system for Genomics N. molecule that incorporating a nucleic acid Hyper-branched polymer of targeting Particularly the tumor environment A1 micrornas and Ltd.,  Kredp- mimics or molecule, which can strongly polyglycerol-amine (PG-NH2) glioblastoma due to the enhanced uses thereof  Ramot At Russo, S. inhibits the improve microRNA stability, permeability and retention sequence and intracellular trafficking as (EPR) Tel-Aviv  Lithwick, 2014 [18] University Y.G. activity of a well as miRNA's silencing Ltd  Satchi- microRNA efficacy, and which further Fainaro, R. exhibits accumulation in

WO2014203189  Ofek, P. tumor and hence can be used in cancer therapy.

Aptamers for The Rich, J. N. N/A Aptamers consisting of a single stranded nucleic acids having 100 Aptamer Treatment Glioblastoma The aptamer specifically A1

tumor initiating Cleveland Kim, Y. nucleotides or less that specifically binds to tumor initiating cancer or diagnosis binds to tumor initiating cells Clinic Hjelmeland, cells are described. cells (TIC) of GBM Foundation A.

2014 [19] WO2014121256

Dual-targeting National Kuo, Y. C. Anticancer The invention proposes a dual-targeting drug carrier, which FA targets FA Treatment Glioblastoma MPEG-PLA nanoparticles

drug carrier and Chung Chang, Y. H. drugs eg. comprises a plurality of methoxy poly(ethylene glycol)-poly(ε- receptor can penetrate the blood A1 method for Cheng etoposide, caprolactone) nanoparticle (MPEG-PLA nanoparticles) each WGA targets brain barrier (BBB) of the fabricating the University carmustine encapsulating at least one anticancer drug, folic acid (FA), and N- carrier and thus, enables same injection, and wheat germ agglutinin (WGA) , wherein FA and WGA are grafted on acetylglucosami the anticancer drugs 2015 [20] doxorubicin the surface of the MPEG-PLA nanoparticles ne of human encapsulated inside to injections brain pass through BBB and microvascular target human

US20150209284 endothelial cells glioblastoma cells (HBMECs) US2012003980 US20140377366 A1 US20120107282 A1 WO2014143765 A1 US20140128337 A1 8 A1 formulations conjugate antibody Anti Tumor Agent Therapeutic Promoter, Differentiation Stem Brain Metastasis Tumour Cancer the Docetaxel Combination Curcuminoids agents therapeutic delivery polymers Biodegradable treatment and treating capable composition Neural

Treatment - EGFR

method

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  Mines School Colorado Co., S. Tokyo University The (INSERM) Medicale Recherche De La National Institut

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Kim, M. Bayet Chollet, C. Barthomeuf, Krebs,        

Kumar, Kaleta, M. Tschoepe, Ino, Todo, K. Miyazawa, Ikushima, K. Miyazono,

S.

- Y. Robert,

M.

U. T.

P.

K. V.

D.

H.

management glioblastoma delivery dual hydrogel within added tic Chemotherapeu antibodies Anti kinase) thymidine simplex e carboxylesteras deaminase, cytosine gene contain engineered genetically cells Neural auristatin Chemotherapy, Sox2 TGF inhibits A  

Docetaxel Curcuminoids

and promotor

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sugar, conjugated binding EGFR (ADC), antibody comprising A stem differentiation by reduces brain A metastases. treatment (Taxotere®, efficacy enhancing use The tumor hydrogel laden placement The (NSCs) sites, and both tumors central A histidine.

differentiation

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invention

cells. tumor

using extracranial/extraspinal of

system resection stable

intracranial/intraspinal

antibody

and

including;

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portion

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anti stem Docetaxel

tumors conjugate

antibody into an antigen for

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EGFR to

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nucleic weight May  

polyesters co glycol) chondroitan GAG hyaluronic glycolic microsphere biodegradable Biodegradable

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Treatment Treatment Treatment Treatment Treatment

Glioblastoma ma medulloblasto Glioma Glioblastoma glioblastoma including Brain glioblastoma. including Tumors

tumors

and

sustained stable localized resected the releas hydrogel The cells tumor gene and delivery effect vessels, through intracranial migrate and both human Genetically (TGF transforming functio promoted tumor The induction angiogenesis progression, turn (PAF) platelet down angiogenesis independent) 1 (Pgp) both Curcumin  

- abnormal hyperproliferative found EGFR A tubulin. polymerization division Auristatin (dependent lso,

. differentiation

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2014 2012 2012 2014 2014

[ [ [ [ [ 25 24 22 21 23 ] ] ] ] ]

US20150094336 US20110124712 A1 US 20110189205 A1 US9044514 B2 A1 receptor "CGRP" related calcitonin activity that using treating Methods thereof nanoparticles conjugates polymer Lipid 2,6 2 dihydro 1 with treating Methods molecules microRNA comprising composition Anti - - yl) oxo -

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peptide - modulates - 1,3

an

(4 -

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gliomas - of peptide

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- amino cancer

gene

agent

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Center Cancer National Rochester University California University The Regents Corporation Celgene

of

Of o

f

Brown, M. Dickerson, Shu, Dong, Xu, Zeldis,         

Kwak, Kim, Kim, Yoo, Yang, Lee, Park, Lee, Park,

T.

J.

D. S. H. T. H. H.

J.

E. J. E.

H. H.

H. H.

J. B.

B. K.

B.

S. J. I.

molecule nucleic MicroRNA acid protein antibody, 2 1     dione piperidine isoindol 1,3 (4 Revimid™

Modulators cancer as receptor CGRP The radioisotopes) as agents D others.) rapamycin temzolomide, as agents anticancer Therapeutic - -

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doxorubicin,

invention

novel

acid - or and 2 -

- 1 antagonist - (and

- (calcitonin , yl) 2,6 or (such (such

125 -

partial

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target

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disease

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gene cancer,

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to

self

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fragment the

characterized

the invention with acid

or or onally

inhibitor

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and/or immunomodulatory and assemble

of or identification

angiogenesis.

to helix

related manage par antisense

protein

include conjugates administered

hypoxia molecule a condition associated of -

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vectors: nucleic

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composition

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composition

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alone the be

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Targeting Passive Antibody     

An ligands receptor somatstatin derivatives somatostatin derivatives, NGR RGD integrin derivatives, B derivatives folic - 12

aptamer.

N/A peptides

acid

or

Treatment Treatment or Treatment Treatment

diagnosis

Brain Glioma multiforme Gliobastoma including B Glioma rain

cancers cancer

include nanoparticle conjuga Lipid treating su second combination can compounds Immunomodulatory metastasis inhibiting angiogenesis, of resulting chromosome homolog (phosphatase the expression can nucleic The  

(“RCP”) component and (“RAMP1”) modifying receptor (“CLR”) calcitonin CGRP Can variant. growth cell capable conditions, Under of would in replicat stimulating conditions, CGRP ch

inactivation - suppress cancer be

peptide as

a be

a te

Glioblastoma replication active

stimulate temozolomide ion

acid

targeting administered Under

in primary

VEGF in modulated f inhibitor

orms antagonist, a microRNA of - invasion

of

like

inhibit deleted

the that - inhibitor,

a

induced is

polymer

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capable

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VEGF tensin PTEN cell which

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2011 2011 2015 2015

[ [ [ [ 29 28 27 26 ] ] ] ]

US20130090321 US 20100129470 US 20110070314 A1 US 20110318334 A1 US 20120157402 A1 US20140066445 A1 A1 A1 of for Taxane tumors treating Methods Kinase Modulating and Composition tumors treating Methods cancer treating Method cancer treating Method

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Yang, Jo, Pharma . Incorporated als, Pharmaceutic Myriad als, Pharmaceutic Tapestry Cao, als, Pharmaceutic Kinex

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Laughlin, G. Hangauer,                     

Yang, Jo, Keppler, S. Valiahdi, Cobb, Baerga, aran, Sheshbarad Modiano, Kurman, Cohn, Ahmed, Marshall, L. Emerson, Tapolsky, J. McChesney, Weetall, Miller, Miao, Hirawat, Davis, Cao,

D.

Y.J.

L.

H.

H.

Y.J. L. A. J. T.

M.

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[ [ [ [ [ [ 35 34 33 32 31 30 ] ] ] ] ] ]

EP20120171160 WO2010095940 A2 US20140161762 A1 US 20130183368 A1 delivery based Glutathione of based for temozolomide Drug methods conjugates P97 gHoPe2 peptides, penetrating and homing between constructs Chimeric

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2013 2010 2014 2013

[ [ [ [ 39 38 37 36 ] ] ] ]

US20130224208 A1 US20110059114 A1 US20150037437 A1 US 20150111831 A1 c Glioma radioresistant the and Compositions treatment Glioma using treating Method these drugs glioma, substance desired delivering method testing method, treatment Glioma ells

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2013 2011 2015 2015

[ [ [ [ 43 42 41 40 ] ] ] ]

US8252338 B2 US9011913 B2 US20110054236 A1 US20140296286 A1 and cancer nanoparticles magnetic functionalized Use targeting and Compositions glioma the specificity with Compounds delivery as Synthetic

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M. Nikanjam, Forte, Engel, Akhtari, David, Yang, Geisert, Yates, Asres, Ahmed, Jones, Patil, Patil, Miller,

R. S.

V. T. D.

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doxorubicin. paclitaxel, oleate, as cancer toxins, gene nucleic siRNA radioisotopes, antibodies, proteins, peptides therapeutic molecules, inorganic molecules, S agents Anti agents Anti OCH X or independently R wherein as The treatment. agents chemotherapeutic be derivatives, tetrahydroisoquinoline categorized compounds The

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2010 2015 2011 2014

[ [ [ [ 47 46 45 44 ] ] ] ]

US 20140221442 A1 US 8795648 B2 US 20140017331 A1 US 7659314 B2 US 20100076092 A1 uses particles copolymer containing Polysaccharide delivery micelles polymeric pH drug brain nanoparticles Lipid multiforme glioblastoma thereof and tol dianhydrogalacti Use drug cytoplasmic effective tripeptide Leu pendant acid) Poly(beta

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Y.

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2014 2014 2014 2010 0202

[ [ [ [ [ 52 51 50 49 48 ] ] ] ] ]

US 20130090467 A1 WO 2011057216 A1 US 20110274749 A1 US20150093399 A1 barriers microvascular endothelial barrier the into targeting compositions Methods thereof methods fc having conjugates CNS device drug bioconjugate Aptamer in targeting selective nanoparticles phosphosilicate of Bioconjugation

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Jefferies,                   

R. Elsayed, K. Shermon, Wagner, Jones, I. McLennan, n, Bloemberge Sharma, T. Morgan, C. Mcgovern, L. Matters, Kaiser, Barth, I. Altinoglu, Smith, Kester, Adair, Brink, G. De J. Gaillard,

J.

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2013 2010 2011 2015

[ [ [ [ 56 55 54 53 ] ] ] ]

 Liu, J. in the body sufficient to allow for the sustained release of a drug and attachment of a for the transportation and uptake of the conjugate into targeted cells. targeting molecule or However, the biopolymer is biocompatible and resorbable. the release profile of a drug. Compositions Angiochem  Castaigne, Any therapeutic Polypeptide-transport vector Transport vector is a lipid vector, a Polypeptide Treatment Glioma or Angiopep is a and methods for Inc. J. P. agent, including conjugates that is capable of nanoparticle, a polyplex, or a vector such as glioblastoma polypeptide capable of the transport of  Demeule, M. RNAi agents, transporting a therapeutic dendrimer. Angiopep-6 crossing the blood-brain

therapeutic  Che, C. polynucleotides agent across the blood-brain barrier or entering one or A1 agents  Regina, A. (e.g., encoding barrier (BBB) or into a cell. more cells via active RNAi agents), The transport vector may targeting. anticancer contain any therapeutic therapeutics, agent, including RNAi 2015 [57] small molecule agents, polynucleotides drugs, (e.g., encoding RNAi polypeptide agents), anticancer US20150174267 therapeutics, therapeutics, small molecule and drugs, polypeptide hydrophobic therapeutics, and agents. hydrophobic agents. Liposomal MedGenesis  Redelmeier, - Therapeutic Non-PEGylated liposomal composition comprising at least one N/A Treatment Glioblastoma  Convection-enhanced Composition for Therapeutix, T. agent such as saturated neutral phospholipid and at least one saturated anionic and delivery.

Convection- Inc.  Luz, M. topoisomerase phospholipid and a therapeutic or diagnostic agent encapsulated diagnosis  Liposomes can be

Enhanced I/II inhibitors therein is used to overcome toxicity associated with high peak drug highly convective in A1 Delivery to the (ex: topotecan) concentration delivered locally via convection enhanced delivery tissues of the central Central Nervous - Diagnostic (CED). nervous system when system agent such as: an anionic lipid 2011 [58]  MRI magnet component is employed  Gadolinium in the formulation in lieu chelate of PEGylation.

US20110274625  Gadodiamide and Rhodamine  Gadodiamide.

Modulation of St. Louis  Banks, W. A therapeutic or The inhibition of Pgp expression would allow increased N/A Treatment Several Antisense inhibition of the blood brain University diagnostic accumulation of chemotherapeutic drugs in the CNS and so diseases function of RNA and DNA A1 A. barrier protein  Kumar, V. B. agent is increase the effectiveness of treating CNS tumor. including encoding blood brain expression  Darling, T. selected from brain cancer. barrier proteins especially  Clayton, R. topotecan, efflux transporter. 2010 [59] conotoxin, gadodiamide or

rhodamine. US20100196393

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